Patient data are sorted by mutation combination frequency.

Reference:	Agostino et al, 2003; [PubMed] 1
Description:	PEO, bilateral ptosis, severe limita- tion of ocular motility, and a mosaic distribution of ragged-red and cytochrome c oxidase–negative fibers in the muscle biopsy. All patients had multiple deletions of muscle mtDNA.
Mutations:	P587L, R227W
SNPs:	T251I
Age group:	adult
Age of Onset: 48, Age of Patient: n/a, Age of Death: n/a

Reference:	Ashley et al, 2008; [PubMed] 2
Description:	Alpers, epilepsy and hepatopathy, onset 5 months of age.
Mutations:	P587L, R232G
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.5, Age of Patient: n/a, Age of Death: n/a

Reference:	Blok et al, 2009; [PubMed] 3
Description:	Exercise intolerance, CPEO, retinitis pigmentosa, diabetes, limb girdle weakness. 2nd patient with cataract and myopathy
Mutations:	A467T, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 51, Age of Death: n/a

Reference:	Di Fonzo et al, 2003; [PubMed] 4
Description:	PEO
Mutations:	P587L, R807P
SNPs:	T251I
Age group:	adult
Age of Onset: 46, Age of Patient: 47, Age of Death: n/a

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Reference:	Di Fonzo et al, 2003; [PubMed] 5
Description:	PEO, axonal sensorimotor polyneuropathy
Mutations:	P587L, R807P
SNPs:	T251I
Age group:	adult
Age of Onset: 60, Age of Patient: 71, Age of Death: n/a

Reference:	Di Fonzo et al, 2003; [PubMed] 6
Description:	PEO, dysphagia
Mutations:	P587L, R807P
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: 52, Age of Death: n/a

Reference:	Ferreira et al, 2011; [PubMed] 7
Description:	Ptosis, oculopharyngeal muscular dystrophy-like, pigmentary retinopathy.
Mutations:	P587L, P648R
SNPs:	T251I
Age group:	adult
Age of Onset: 59, Age of Patient: 67, Age of Death: n/a

Reference:	Ferrari et al, 2005; [PubMed] 8
Description:	Infantile hepatocerebral, presented at 3 months as hypotonia followed by mtDNA depletion in liver, dementia, and death at 6 months by ventilatory insufficiency.
Mutations:	P587L, R232G
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 0.5

Reference:	Gonzalez-Vioque et al, 2006; [PubMed] 9
Description:	PEO with ptosis, mild atrial hypertrophy. Sister had PEO.
Mutations:	M603L, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 61, Age of Patient: 65, Age of Death: n/a

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Reference:	Horvath et al, 2006; [PubMed] 10
Description:	PEO
Mutations:	P587L, R227W
SNPs:	T251I
Age group:	adult
Age of Onset: 48, Age of Patient: n/a, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 11
Description:	PEO with myopathy
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	adult
Age of Onset: 62, Age of Patient: 70, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 12
Description:	PEO with myopathy
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 56, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 13
Description:	PEO with myopathy, chronic bronchitis.
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	adult
Age of Onset: 63, Age of Patient: n/a, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 14
Description:	PEO, Neuropathy. Affect sibling.
Mutations:	L304R, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 60, Age of Patient: 68, Age of Death: n/a

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Reference:	Horvath et al, 2006; [PubMed] 15
Description:	PEO, myopathy, ataxia.
Mutations:	L304R, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: 74, Age of Death: n/a

Reference:	Lamantea et al, 2002; [PubMed] 16
Description:	PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle.
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:	Lamantea et al, 2002; [PubMed] 17
Description:	PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle.
Mutations:	P587L
SNPs:	PNF, T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:	Lamantea et al, 2002; [PubMed] 18
Description:	PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle.
Mutations:	P587L, R309L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:	Sarzi et al, 2007; [PubMed] 19
Description:	Alpers, trunk hypotonia, seizures at 4 months, RC deficiency in liver. 28% mtDNA copy number in liver.
Mutations:	C224Y, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.3, Age of Patient: n/a, Age of Death: n/a

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Reference:	Stewart et al, 2009; [PubMed] 20
Description:	Mild bilateral ptosis, PEO.
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	adult
Age of Onset: 41, Age of Patient: n/a, Age of Death: n/a

Reference:	Stewart et al, 2009; [PubMed] 21
Description:	PEO, ptosis, proximal weakness, multiple mtDNA deletions-LPCR. 25% COX-deficient fibers
Mutations:	A467T, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: n/a, Age of Death: n/a

Reference:	Taanman et al, 2009; [PubMed] 22
Description:	Vomiting, FTT, hypotonic, lactic acidemia, hypoglycemia, bilateral dense cataracts, hepatomegaly, jaundice, septicemia. infantile hepatocerebral mtDNA depletion. Mother with E1136K allele reported as asymptomatic. Father with T251I/P587L allele reported as asymptomatic.
Mutations:	E1136K, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.01, Age of Patient: n/a, Age of Death: 0.5

Reference:	Tang et al, 2011; [PubMed] 23
Description:	N/A (as reported in Tang 2011 JMG)
Mutations:	N1157S, P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: n/a, Age of Patient: 9, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 24
Description:	Ocular bulbar weakness, peripheral neuropathy, muscle weakness, CPEO, ptosis, hypothyroidism, abnormal muscle histology, abnormal muscle ultrastructure, large mitochondrial proliferation, ragged red fibers. 96% mtDNA copy number in blood. Patient II-44.
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 81, Age of Death: n/a

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Reference:	Tang et al, 2011; [PubMed] 25
Description:	Peripheral neuropathy, exercise intolerance, muscle cramps after exercise, easy fatigability, arrythmia, CPEO, abnormal EMG/NCV, ptosis, cataract, abnormal muscle histology, abnormal muscle ultrastructure, COX deficiency, ragged red fibers. 123% mtDNA copy number in blood.
Mutations:	H932Y, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 31, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 26
Description:	Peripheral neuropathy, ptosis, muscle weakness, CPK abnormalities. 77% mtDNA copy number in blood.
Mutations:	H932Y, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 41, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 27
Description:	Stroke/ischaemic episodes, peripheral neuropathy, CPEO, abnormal EMG/NCV, ptosis, muscle weakness, headache/migraine. 167% mtDNA copy number in blood.
Mutations:	K1191N, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 39, Age of Death: n/a

Reference:	Van Goethem et al, 2003c; [PubMed] 28
Description:	MNGIE-like, presented with GI symptoms, ptosis, neuropathy, muscle weakness.
Mutations:	N864S, P587L
SNPs:	T251I
Age group:	juvenile
Age of Onset: 15, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 29
Description:	Alpers
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.5, Age of Patient: n/a, Age of Death: n/a

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Reference:	Wong et al, 2008; [PubMed] 30
Description:	Developmental delay, dementia, lactic acidosis, microcephaly, FTT, hearing loss, abnormal MRI.
Mutations:	P587L, R853Q
SNPs:	T251I
Age group:	infantile
Age of Onset: n/a, Age of Patient: 0.2, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 31
Description:	Developmental delay/dementia, liver dysfunction, lactic acidosis, fatigue, pancreatitis, cyclic vomiting.
Mutations:	K1191R, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a

Reference:	Kollberg et al, 2005; [PubMed] 32
Description:	PEO, severe ophthalmoplegia and ptosis, which appeared insidiously and had been present clinically since the age of 55. Muscle biopsy at age 68 revealed mitochondrial myopathy, as well as muscle inflammation with granulomas. multiple mtDNA deletions in muscle tissue.
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 55, Age of Patient: 75, Age of Death: n/a

Reference:	Burusnukul and de los Reyes, 2009; [PubMed] 33
Description:	Global developmental delay, Central hypotonia, Torticollis, feeding difficulty at birth, myoclonic seizure, horizontal nystagmus, Intermittent estropia, Abnormal MRI
Mutations:	P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.4, Age of Patient: n/a, Age of Death: n/a

Reference:	Lutz et al, 2009; [PubMed] 34
Description:	Presented with feeding difficulties and hypotonia, At 4.5 months of age the patient contracted an influenza A infection. Concurrently she experienced hepatomegaly associated with severe hypoglycemia, Abnormalities in liver synthetic function, elevations in liver hepatocellular enzymes, elevated cerebrospinal fluid (CSF) protein, severely reduced mtDNA (3%) in liver. liver failure. She showed signs of ongoing respiratory difficulty, pancreatitis, and renal tubulopathy
Mutations:	K1191R, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.166, Age of Patient: 0.416, Age of Death: 0.458

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Reference:	Weiss and Saneto, 2010; [PubMed] 35
Description:	progressively droopy eyelids, double vision, gait instability, proximal arm weakness, ragged red and ragged blue (succinate dehydrogenase–positive) fibers in about 3% and 6% of all muscle fibers, bilateral ptosis, diplopia, dysarthria, myopathy involving the facial muscles, sensory ataxic polyneuropathy
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 80, Age of Death: n/a

Reference:	Amiot et al, 2009; [PubMed] 36
Description:	Peripheral neuropathy, PEO, ataxia, epilepsy, fatty liver
Mutations:	D1184N, P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: 9, Age of Patient: n/a, Age of Death: 33

Reference:	Amiot et al, 2009; [PubMed] 37
Description:	Peripheral neuropathy, PEO, fatty liver
Mutations:	D1184N, P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: 9, Age of Patient: n/a, Age of Death: 30

Reference:	Aitken et al, 2009; [PubMed] 38
Description:	Progressively blurred vision, diplopia, and longstanding bilateral ptosis (adPEO). She described occasional choking episodes after eating as well as fatigue and shortness of breath after minimal exertion. Lower limb examination revealed symmetric proximal limb weakness with reduced reflexes and flexor plantars. Tan- dem gait was hesitant. The initial differential diagnosis included Graves thyroid eye disease, a neuromuscular junction disor- der (myasthenia gravis or botulism), oculopharyngeal muscular dystrophy, Miller Fisher variant of Guillain-Barre syndrome, and progressive muscular dystrophy. Borderline myopathy. The muscle biopsy showed 13% cytochrome c ox- idase (COX)–deficient fibers, significant numbers of ragged red fibers but no excess of lipid or glycogen accumulation, and subsarcolemmal accumulation of abnormal mitochondria suggestive of a mitochondrial cytopathy. The patient presented 10 months later with an un- pleasant “jumping” sensation in her feet when at rest which was relieved by movement. Symptoms were worse at night and she also described sudden involuntary movements of her lower limbs (restless legs syndrome, RLS).
Mutations:	P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 53, Age of Patient: 58, Age of Death: n/a

Reference:	Hanisch et al, 2014; [PubMed] 39
Description:	Pareses, ptosis, ataxia, sensory neoropathy, motor neuropathy, axonal neuropathy, demyelinating neuropathy.
Mutations:	P587L, R869Q
SNPs:	T251I
Age group:	adult
Age of Onset: 29, Age of Patient: 34, Age of Death: n/a

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Reference:	Harris et al, 2010; [PubMed] 40
Description:	Progressive ataxia, asymmetrical right ophthalmoplegia and encephalopathy. Seizures. Loss of extraocular movement on the right and right arm and leg spasticity and hyperreflexia. Elevated lactate level, a markedly depressed N-acetylaspartate level, and a markedly elevated choline level. Steroid-induced hyperglycemia. Progressive acute disseminated encephalomyelitis (ADEM).
Mutations:	P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: n/a, Age of Patient: 4, Age of Death: 4.75

Reference:	Lovan et al, 2013; [PubMed] 41
Description:	diabetes mellitus 2, congestive heart failure, hypothyroidism, hypertension, depression with psychotic features and gastric bypass surgery. gait difficulties, cognitive impairment, ophthalmoplegia, resting tremor and peripheral neuropathy. Shooting pains and numbness in her lower extremities, occasional rectal incontinence. Presyncopal dizziness. Complicated diabetic retinopathy. sensory ataxia secondary to a sensorimotor polyneuropathy, chronic supranuclear ophthalmoplegia, and a resting tremor of her right hand. bilateral ptosis and marked temporal muscle wasting. Her sensory examination found loss of pinprick sensation, temperature and vibration bilaterally up to her hips. She had bilateral vibration loss at her fingertips. She had loss of proprioception at her toes. She had bilateral dysdiadochokinesia with significant ataxia on finger to nose testing. Arreflexic in her lower extremities. On cognitive testing she was found to have moderate dementia with significant deficits in registration and construction as well as ideomotor apraxia.
Mutations:	A467T, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 55, Age of Patient: 60, Age of Death: n/a

Reference:	Scuderi et al, 2015; [PubMed] 42
Description:	He presented migraine by age 7 and complained of fatigue during exercise by age 12. mild diffuse muscle hypotonia and flat feet. ptosis at 14. Brain MRI showed mild white matter hyperintensity.
Mutations:	P587L
SNPs:	P116Q, T251I
Age group:	childhood
Age of Onset: 7, Age of Patient: 14, Age of Death: n/a

Reference:	Scuderi et al, 2015; [PubMed] 43
Description:	Presented deafness from childhood. migraine and fatigue. On neurological examination she had mild diffuse muscle weakness. Audiometric examination disclosed neurosensorial hypoacusia. mild anxiety with specific phobias concerning indoor environment and crowd.
Mutations:	P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 29, Age of Patient: 37, Age of Death: n/a

Reference:	Scuderi et al, 2015; [PubMed] 44
Description:	delayed psychomotor development. At age 3, neurological examination showed muscular hypotonia, joint laxity, absent deep tendon reflexes, broadbased gait, scapular winging, accentuation of lumbar lordosis and flat feet. intellectual disability. progressive cognitive impairment. mild myopathy.
Mutations:	P587L
SNPs:	P116Q, T251I
Age group:	childhood
Age of Onset: 3, Age of Patient: 8, Age of Death: n/a

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Reference:	Scuderi et al, 2015; [PubMed] 45
Description:	leg pain after physical activity. mild diffuse muscle hypotonia, hypotrophy, mild diffuse muscle weakness, joint laxity, scapular winging and increase of lumbar lordosis. Borderline intellectual functioning.
Mutations:	P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: n/a, Age of Patient: 10, Age of Death: n/a

Reference:	Stewart et al, 2011; [PubMed] 46
Description:	Alpers. nocturnal nausea followed by loss of consciousness without motor relinquishing. obsessive–compulsive disorder.
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	juvenile
Age of Onset: 16, Age of Patient: 26, Age of Death: n/a

Reference:	Del Bo et al, 2003; [PubMed] 47
Description:	PEO, complicated by dysphagia, myopathy.
Mutations:	P587L
SNPs:	PNF, T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 52, Age of Death: n/a

Reference:	Del Bo et al, 2003; [PubMed] 48
Description:	PEO, complicated by dysphagia, myopathy.
Mutations:	P587L, R807P
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 71, Age of Death: n/a

Reference:	Miguel et al, 2014; [PubMed] 49
Description:	slowly progressive bilateral blepharoptosis, severe PEO, dysphagia, facial diparesis and exercise intolerance, presented, at the age of 60, with left-dominant postural tremor, reduced left arm swing during gait, postural instability, axonal sensory polyneuropathy, CT showed diffuse cerebral atrophy. Parkinsons.
Mutations:	P587L
SNPs:	PNF, T251I
Age group:	adult
Age of Onset: 46, Age of Patient: 66, Age of Death: n/a

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Reference:	Ashley et al, 2008; [PubMed] 50
Description:	Encephalopathy onset 16 years of age, presented with epilepsy.
Mutations:	P587L, P589L, W748S
Age group:	juvenile
Age of Onset: 16, Age of Patient: n/a, Age of Death: n/a

Reference:	Tzoulis et al, 2009; [PubMed] 51
Description:	PEO, ptosis, muscle fatigue, diplopia, a mild external ophthalmoplegia affecting horizontal, but not vertical gaze. Tendonreflexes were diminished in the lower extremities and a distal sensory defect in stocking distribution was seen.
Mutations:	P587L, W748S
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: 50, Age of Death: n/a

Reference:	Ylönen et al, 2013; [PubMed] 52
Description:	Akinetic-rigid Parkinsons. impaired balance, freezing, and increased salivation. Constipation and muscle cramps. He had arterial hypertension and mild normocytic anemia. cytochrome c oxidase-negative muscle fibers.
Mutations:	P587L, W748S
SNPs:	E1142G, T251I
Age group:	adult
Age of Onset: 49, Age of Patient: 65, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 53
Description:	PEO with myopathy
Mutations:	P587L, V1106I
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 35, Age of Death: n/a

Patient data are sorted by mutation combination frequency.

Reference:	Blok et al, 2009; [PubMed] 1
Description:	Exercise intolerance, CPEO, retinitis pigmentosa, diabetes, limb girdle weakness. 2nd patient with cataract and myopathy
Mutations:	A467T, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 51, Age of Death: n/a

Reference:	Gonzalez-Vioque et al, 2006; [PubMed] 2
Description:	PEO with ptosis, mild atrial hypertrophy. Sister had PEO.
Mutations:	M603L, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 61, Age of Patient: 65, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 3
Description:	PEO, Neuropathy. Affect sibling.
Mutations:	L304R, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 60, Age of Patient: 68, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 4
Description:	PEO, myopathy, ataxia.
Mutations:	L304R, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: 74, Age of Death: n/a

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Reference:	Lamantea et al, 2002; [PubMed] 5
Description:	PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle.
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:	Sarzi et al, 2007; [PubMed] 6
Description:	Alpers, trunk hypotonia, seizures at 4 months, RC deficiency in liver. 28% mtDNA copy number in liver.
Mutations:	C224Y, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.3, Age of Patient: n/a, Age of Death: n/a

Reference:	Stewart et al, 2009; [PubMed] 7
Description:	PEO, ptosis, proximal weakness, multiple mtDNA deletions-LPCR. 25% COX-deficient fibers
Mutations:	A467T, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: n/a, Age of Death: n/a

Reference:	Taanman et al, 2009; [PubMed] 8
Description:	Vomiting, FTT, hypotonic, lactic acidemia, hypoglycemia, bilateral dense cataracts, hepatomegaly, jaundice, septicemia. infantile hepatocerebral mtDNA depletion. Mother with E1136K allele reported as asymptomatic. Father with T251I/P587L allele reported as asymptomatic.
Mutations:	E1136K, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.01, Age of Patient: n/a, Age of Death: 0.5

Reference:	Tang et al, 2011; [PubMed] 9
Description:	N/A (as reported in Tang 2011 JMG)
Mutations:	N1157S, P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: n/a, Age of Patient: 9, Age of Death: n/a

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Reference:	Tang et al, 2011; [PubMed] 10
Description:	Ocular bulbar weakness, peripheral neuropathy, muscle weakness, CPEO, ptosis, hypothyroidism, abnormal muscle histology, abnormal muscle ultrastructure, large mitochondrial proliferation, ragged red fibers. 96% mtDNA copy number in blood. Patient II-44.
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 81, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 11
Description:	Peripheral neuropathy, exercise intolerance, muscle cramps after exercise, easy fatigability, arrythmia, CPEO, abnormal EMG/NCV, ptosis, cataract, abnormal muscle histology, abnormal muscle ultrastructure, COX deficiency, ragged red fibers. 123% mtDNA copy number in blood.
Mutations:	H932Y, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 31, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 12
Description:	Peripheral neuropathy, ptosis, muscle weakness, CPK abnormalities. 77% mtDNA copy number in blood.
Mutations:	H932Y, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 41, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 13
Description:	Stroke/ischaemic episodes, peripheral neuropathy, CPEO, abnormal EMG/NCV, ptosis, muscle weakness, headache/migraine. 167% mtDNA copy number in blood.
Mutations:	K1191N, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 39, Age of Death: n/a

Reference:	Van Goethem et al, 2003c; [PubMed] 14
Description:	MNGIE-like, presented with GI symptoms, ptosis, neuropathy, muscle weakness.
Mutations:	N864S, P587L
SNPs:	T251I
Age group:	juvenile
Age of Onset: 15, Age of Patient: n/a, Age of Death: n/a

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Reference:	Wong et al, 2008; [PubMed] 15
Description:	Alpers
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.5, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 16
Description:	Developmental delay/dementia, liver dysfunction, lactic acidosis, fatigue, pancreatitis, cyclic vomiting.
Mutations:	K1191R, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a

Reference:	Kollberg et al, 2005; [PubMed] 17
Description:	PEO, severe ophthalmoplegia and ptosis, which appeared insidiously and had been present clinically since the age of 55. Muscle biopsy at age 68 revealed mitochondrial myopathy, as well as muscle inflammation with granulomas. multiple mtDNA deletions in muscle tissue.
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 55, Age of Patient: 75, Age of Death: n/a

Reference:	Burusnukul and de los Reyes, 2009; [PubMed] 18
Description:	Global developmental delay, Central hypotonia, Torticollis, feeding difficulty at birth, myoclonic seizure, horizontal nystagmus, Intermittent estropia, Abnormal MRI
Mutations:	P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.4, Age of Patient: n/a, Age of Death: n/a

Reference:	Lutz et al, 2009; [PubMed] 19
Description:	Presented with feeding difficulties and hypotonia, At 4.5 months of age the patient contracted an influenza A infection. Concurrently she experienced hepatomegaly associated with severe hypoglycemia, Abnormalities in liver synthetic function, elevations in liver hepatocellular enzymes, elevated cerebrospinal fluid (CSF) protein, severely reduced mtDNA (3%) in liver. liver failure. She showed signs of ongoing respiratory difficulty, pancreatitis, and renal tubulopathy
Mutations:	K1191R, P587L
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.166, Age of Patient: 0.416, Age of Death: 0.458

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Reference:	Weiss and Saneto, 2010; [PubMed] 20
Description:	progressively droopy eyelids, double vision, gait instability, proximal arm weakness, ragged red and ragged blue (succinate dehydrogenase–positive) fibers in about 3% and 6% of all muscle fibers, bilateral ptosis, diplopia, dysarthria, myopathy involving the facial muscles, sensory ataxic polyneuropathy
Mutations:	G848S, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 80, Age of Death: n/a

Reference:	Amiot et al, 2009; [PubMed] 21
Description:	Peripheral neuropathy, PEO, ataxia, epilepsy, fatty liver
Mutations:	D1184N, P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: 9, Age of Patient: n/a, Age of Death: 33

Reference:	Amiot et al, 2009; [PubMed] 22
Description:	Peripheral neuropathy, PEO, fatty liver
Mutations:	D1184N, P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: 9, Age of Patient: n/a, Age of Death: 30

Reference:	Aitken et al, 2009; [PubMed] 23
Description:	Progressively blurred vision, diplopia, and longstanding bilateral ptosis (adPEO). She described occasional choking episodes after eating as well as fatigue and shortness of breath after minimal exertion. Lower limb examination revealed symmetric proximal limb weakness with reduced reflexes and flexor plantars. Tan- dem gait was hesitant. The initial differential diagnosis included Graves thyroid eye disease, a neuromuscular junction disor- der (myasthenia gravis or botulism), oculopharyngeal muscular dystrophy, Miller Fisher variant of Guillain-Barre syndrome, and progressive muscular dystrophy. Borderline myopathy. The muscle biopsy showed 13% cytochrome c ox- idase (COX)–deficient fibers, significant numbers of ragged red fibers but no excess of lipid or glycogen accumulation, and subsarcolemmal accumulation of abnormal mitochondria suggestive of a mitochondrial cytopathy. The patient presented 10 months later with an un- pleasant “jumping” sensation in her feet when at rest which was relieved by movement. Symptoms were worse at night and she also described sudden involuntary movements of her lower limbs (restless legs syndrome, RLS).
Mutations:	P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 53, Age of Patient: 58, Age of Death: n/a

Reference:	Harris et al, 2010; [PubMed] 24
Description:	Progressive ataxia, asymmetrical right ophthalmoplegia and encephalopathy. Seizures. Loss of extraocular movement on the right and right arm and leg spasticity and hyperreflexia. Elevated lactate level, a markedly depressed N-acetylaspartate level, and a markedly elevated choline level. Steroid-induced hyperglycemia. Progressive acute disseminated encephalomyelitis (ADEM).
Mutations:	P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: n/a, Age of Patient: 4, Age of Death: 4.75

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Reference:	Lovan et al, 2013; [PubMed] 25
Description:	diabetes mellitus 2, congestive heart failure, hypothyroidism, hypertension, depression with psychotic features and gastric bypass surgery. gait difficulties, cognitive impairment, ophthalmoplegia, resting tremor and peripheral neuropathy. Shooting pains and numbness in her lower extremities, occasional rectal incontinence. Presyncopal dizziness. Complicated diabetic retinopathy. sensory ataxia secondary to a sensorimotor polyneuropathy, chronic supranuclear ophthalmoplegia, and a resting tremor of her right hand. bilateral ptosis and marked temporal muscle wasting. Her sensory examination found loss of pinprick sensation, temperature and vibration bilaterally up to her hips. She had bilateral vibration loss at her fingertips. She had loss of proprioception at her toes. She had bilateral dysdiadochokinesia with significant ataxia on finger to nose testing. Arreflexic in her lower extremities. On cognitive testing she was found to have moderate dementia with significant deficits in registration and construction as well as ideomotor apraxia.
Mutations:	A467T, P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 55, Age of Patient: 60, Age of Death: n/a

Reference:	Scuderi et al, 2015; [PubMed] 26
Description:	He presented migraine by age 7 and complained of fatigue during exercise by age 12. mild diffuse muscle hypotonia and flat feet. ptosis at 14. Brain MRI showed mild white matter hyperintensity.
Mutations:	P587L
SNPs:	P116Q, T251I
Age group:	childhood
Age of Onset: 7, Age of Patient: 14, Age of Death: n/a

Reference:	Scuderi et al, 2015; [PubMed] 27
Description:	Presented deafness from childhood. migraine and fatigue. On neurological examination she had mild diffuse muscle weakness. Audiometric examination disclosed neurosensorial hypoacusia. mild anxiety with specific phobias concerning indoor environment and crowd.
Mutations:	P587L
SNPs:	T251I
Age group:	adult
Age of Onset: 29, Age of Patient: 37, Age of Death: n/a

Reference:	Scuderi et al, 2015; [PubMed] 28
Description:	delayed psychomotor development. At age 3, neurological examination showed muscular hypotonia, joint laxity, absent deep tendon reflexes, broadbased gait, scapular winging, accentuation of lumbar lordosis and flat feet. intellectual disability. progressive cognitive impairment. mild myopathy.
Mutations:	P587L
SNPs:	P116Q, T251I
Age group:	childhood
Age of Onset: 3, Age of Patient: 8, Age of Death: n/a

Reference:	Scuderi et al, 2015; [PubMed] 29
Description:	leg pain after physical activity. mild diffuse muscle hypotonia, hypotrophy, mild diffuse muscle weakness, joint laxity, scapular winging and increase of lumbar lordosis. Borderline intellectual functioning.
Mutations:	P587L
SNPs:	T251I
Age group:	childhood
Age of Onset: n/a, Age of Patient: 10, Age of Death: n/a

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Reference:	Rouzier et al, 2013; [PubMed] 30
Description:	CPEO, multiple mtDNa deletions.
Mutations:	G848S
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: n/a, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 31
Description:	PEO with myopathy
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	adult
Age of Onset: 62, Age of Patient: 70, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 32
Description:	PEO with myopathy
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 56, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 33
Description:	PEO with myopathy, chronic bronchitis.
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	adult
Age of Onset: 63, Age of Patient: n/a, Age of Death: n/a

Reference:	Stewart et al, 2009; [PubMed] 34
Description:	Mild bilateral ptosis, PEO.
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	adult
Age of Onset: 41, Age of Patient: n/a, Age of Death: n/a

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Reference:	Stewart et al, 2011; [PubMed] 35
Description:	Alpers. nocturnal nausea followed by loss of consciousness without motor relinquishing. obsessive–compulsive disorder.
Mutations:	P587L, P587L
SNPs:	T251I, T251I
Age group:	juvenile
Age of Onset: 16, Age of Patient: 26, Age of Death: n/a

Reference:	Di Fonzo et al, 2003; [PubMed] 36
Description:	PEO
Mutations:	P587L, R807P
SNPs:	T251I
Age group:	adult
Age of Onset: 46, Age of Patient: 47, Age of Death: n/a

Reference:	Di Fonzo et al, 2003; [PubMed] 37
Description:	PEO, axonal sensorimotor polyneuropathy
Mutations:	P587L, R807P
SNPs:	T251I
Age group:	adult
Age of Onset: 60, Age of Patient: 71, Age of Death: n/a

Reference:	Di Fonzo et al, 2003; [PubMed] 38
Description:	PEO, dysphagia
Mutations:	P587L, R807P
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: 52, Age of Death: n/a

Reference:	Del Bo et al, 2003; [PubMed] 39
Description:	PEO, complicated by dysphagia, myopathy.
Mutations:	P587L, R807P
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 71, Age of Death: n/a

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Reference:	Lamantea et al, 2002; [PubMed] 40
Description:	PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle.
Mutations:	P587L
SNPs:	PNF, T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:	Del Bo et al, 2003; [PubMed] 41
Description:	PEO, complicated by dysphagia, myopathy.
Mutations:	P587L
SNPs:	PNF, T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 52, Age of Death: n/a

Reference:	Miguel et al, 2014; [PubMed] 42
Description:	slowly progressive bilateral blepharoptosis, severe PEO, dysphagia, facial diparesis and exercise intolerance, presented, at the age of 60, with left-dominant postural tremor, reduced left arm swing during gait, postural instability, axonal sensory polyneuropathy, CT showed diffuse cerebral atrophy. Parkinsons.
Mutations:	P587L
SNPs:	PNF, T251I
Age group:	adult
Age of Onset: 46, Age of Patient: 66, Age of Death: n/a

Reference:	Agostino et al, 2003; [PubMed] 43
Description:	PEO, bilateral ptosis, severe limita- tion of ocular motility, and a mosaic distribution of ragged-red and cytochrome c oxidase–negative fibers in the muscle biopsy. All patients had multiple deletions of muscle mtDNA.
Mutations:	P587L, R227W
SNPs:	T251I
Age group:	adult
Age of Onset: 48, Age of Patient: n/a, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 44
Description:	PEO
Mutations:	P587L, R227W
SNPs:	T251I
Age group:	adult
Age of Onset: 48, Age of Patient: n/a, Age of Death: n/a

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Reference:	Ashley et al, 2008; [PubMed] 45
Description:	Alpers, epilepsy and hepatopathy, onset 5 months of age.
Mutations:	P587L, R232G
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.5, Age of Patient: n/a, Age of Death: n/a

Reference:	Ferrari et al, 2005; [PubMed] 46
Description:	Infantile hepatocerebral, presented at 3 months as hypotonia followed by mtDNA depletion in liver, dementia, and death at 6 months by ventilatory insufficiency.
Mutations:	P587L, R232G
SNPs:	T251I
Age group:	infantile
Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 0.5

Reference:	Tzoulis et al, 2009; [PubMed] 47
Description:	PEO, ptosis, muscle fatigue, diplopia, a mild external ophthalmoplegia affecting horizontal, but not vertical gaze. Tendonreflexes were diminished in the lower extremities and a distal sensory defect in stocking distribution was seen.
Mutations:	P587L, W748S
SNPs:	T251I
Age group:	adult
Age of Onset: 45, Age of Patient: 50, Age of Death: n/a

Reference:	Ylönen et al, 2013; [PubMed] 48
Description:	Akinetic-rigid Parkinsons. impaired balance, freezing, and increased salivation. Constipation and muscle cramps. He had arterial hypertension and mild normocytic anemia. cytochrome c oxidase-negative muscle fibers.
Mutations:	P587L, W748S
SNPs:	E1142G, T251I
Age group:	adult
Age of Onset: 49, Age of Patient: 65, Age of Death: n/a

Reference:	Horvath et al, 2006; [PubMed] 49
Description:	PEO with myopathy
Mutations:	P587L, V1106I
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: 35, Age of Death: n/a

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Reference:	Ferreira et al, 2011; [PubMed] 50
Description:	Ptosis, oculopharyngeal muscular dystrophy-like, pigmentary retinopathy.
Mutations:	P587L, P648R
SNPs:	T251I
Age group:	adult
Age of Onset: 59, Age of Patient: 67, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 51
Description:	Developmental delay, dementia, lactic acidosis, microcephaly, FTT, hearing loss, abnormal MRI.
Mutations:	P587L, R853Q
SNPs:	T251I
Age group:	infantile
Age of Onset: n/a, Age of Patient: 0.2, Age of Death: n/a

Reference:	Hanisch et al, 2014; [PubMed] 52
Description:	Pareses, ptosis, ataxia, sensory neoropathy, motor neuropathy, axonal neuropathy, demyelinating neuropathy.
Mutations:	P587L, R869Q
SNPs:	T251I
Age group:	adult
Age of Onset: 29, Age of Patient: 34, Age of Death: n/a

Reference:	Lamantea et al, 2002; [PubMed] 53
Description:	PEO. cytochrome c oxidase negative ragged red fibers, and multiple mtDNA deletions in skeletal muscle.
Mutations:	P587L, R309L
SNPs:	T251I
Age group:	adult
Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Patient data are sorted by mutation combination frequency.

Reference:	Ashley et al, 2008; [PubMed] 1
Description:	Epilepsy, ataxia
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 16, Age of Patient: n/a, Age of Death: n/a

Reference:	Stewart et al, 2009; [PubMed] 2
Description:	Alpers, Encephalopathy, liver failure.
Mutations:	A467T, A467T
Age group:	infantile
Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a

Reference:	Stewart et al, 2009; [PubMed] 3
Description:	PEO, ataxia, ataxic sensory axonal neuropathy, dysarthria, multiple mtDNA deletions. 10% COX deficient fibers, 2% RRF.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 30, Age of Patient: n/a, Age of Death: n/a

Reference:	Stewart et al, 2009; [PubMed] 4
Description:	PEO, ataxia, seizures, encephalopathy, ptosis, sensory neuropathy, mtDNA multiple deletions. 20% COX deficient fibers, 3% ragged red fibers.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 12, Age of Patient: n/a, Age of Death: n/a

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Reference:	Tang et al, 2011; [PubMed] 5
Description:	Age 19.6, developmental delay, after 18 years, rapid onset of muscle weakness, ataxia, myoclonic seizures, optic atrophy, diplopia, dysarthria. 102% mtDNA copy number in blood.
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 18, Age of Patient: 20, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 6
Description:	Ataxia, peripheral neuropathy, muscle weakness, easy fatigability, CPEO, abnormal EMG/NCV, ptosis, delayed gastric emptying, diarrhoea, constipation, lactic acidosis, abnormal muscle ultratstructure, ragged red fibers. 75% mtDNA copy number in blood.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: n/a, Age of Patient: 46, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 7
Description:	Stroke/ischaemic episodes, ataxia, seizures, myoclonic seizures, peripheral neuropathy, CPEO. 114% mtDNA copy number in blood.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: n/a, Age of Patient: 40, Age of Death: n/a

Reference:	Winterthun et al, 2005; [PubMed] 8
Description:	At age 17, she had an epileptic seizure preceded by tiredness and blurred vision. Visual blurring and poor memory persisted and 5 days later she developed status epilepticus with a focal start in the right arm. Examination showed horizontal nystagmus that did not settle, normal eye movements, and normal peripheral findings except that the deep tendon reflexes were recorded as weak. She returned 3 years later at age 20 with headache and unsteadiness. myoclonus and progressive ophthalmoplegia, ataxia, frequent myoclonic jerks. Cognitive dysfunction, axonal neuropathy.
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 17, Age of Patient: 49, Age of Death: n/a

Reference:	Winterthun et al, 2005; [PubMed] 9
Description:	Headache, tremor, sensory ataxia, dysarthria, nystagmus, ophthalmoplegia, cognitive dysfunction, axonal neuropathy, demyelinating neuropathy. She had headaches with preceding visual symptoms diagnosed as migraine that started at age 16. Episodic, involuntary jerking movements involving head and hands developed soon after. At age 18 she had two tonic clonic seizures preceded by poor concentration, confusion, and increased involuntary movements. Examination recorded titubation and myoclonus of the arms diminished reflexes in the legs, and reduced proprioception at the hallux. She has recurrent seizures and frequent headaches. At age 26 cerebellar and sensory ataxia, dysarthria, limita- tion of horizontal and vertical eye movements, and absent reflexes were recorded. COX negative fibers. At age 37 she was admitted with status epilepticus preceded by headache and visual symptoms in the right visual field. She remains ataxic but ambulant with assistance.
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 16, Age of Patient: 39, Age of Death: n/a

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Reference:	Winterthun et al, 2005; [PubMed] 10
Description:	Headache, tremor. At age 20, he developed unsteadiness and dizziness. Examination showed upper limb tremor and myoclonus, and titubation. At age 31 limitation of horizontal eye movements was recorded; muscle biopsy was reported as showing no ragged red fibers. Subsequently, he developed limb and truncal ataxia, worsening ophthalmoplegia, pain in his extremities with glove and stocking sensory loss, particularly affecting proprioception, and sudden falls with altered consciousness that responded to anticonvulsant treatment. Sensory ataxia. axonal neuropathy, ophthalmoplegia, demyelination neuropathy, cognitive dysfunction, focal occipital epilepsy.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 10, Age of Patient: 43, Age of Death: n/a

Reference:	Winterthun et al, 2005; [PubMed] 11
Description:	This man developed epilepsy at age 5. At age 16 he developed unsteadiness and was euphoric. He had a right-sided divergent squint and difficulties on upgaze when the right eye would drift outward. Eye movements were otherwise full. There were horizontal nystagmus, absent tendon reflexes, and loss of proprioception distally in the legs. His gait was ataxic. Positive Romberg sign. At age 20 mild dysarthria was noted. Subsequently, he developed finger dysmetria, dysdiadochokinesis and myoclonus involving his arms, diarrhea, weight loss and cachexia, and ophthalmoplegia. Between the ages of 35 and 54 years he had infrequent seizures, but at age 55 he developed treatment-resistant status epilepticus and died. Cognitive dysfunction, axonal neuropathy, status epilepticus.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 5, Age of Patient: n/a, Age of Death: 55

Reference:	Wong et al, 2008; [PubMed] 12
Description:	Onset 23 years with ataxia, neuropathy, hearing loss, seizures, and VPA liver failure. From "Saneto et al, 2010": Sensory neuropathy, ataxia, seizure onset at 15 years, simple partial seizure and epilepsia partialis continua myoclonus, VPA treatment caused liver failure after 3 months, progressive encephalopathy, Sensorineural hearing loss, dysmetria, intention tremor, hypotonia
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 15, Age of Patient: 23, Age of Death: 23.5

Reference:	Wong et al, 2008; [PubMed] 13
Description:	Onset 32 years with neuropathy, myopathy, SANDO, PEO.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 32, Age of Patient: n/a, Age of Death: n/a

Reference:	Nguyen et al, 2005; [PubMed] 14
Description:	Refractory seizures, psychomotor regression, liver disease, presented with epilepsia partialis continua, Transient lactic acidemia
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 8.5, Age of Patient: n/a, Age of Death: 9

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Reference:	Milone et al, 2011; [PubMed] 15
Description:	progressive bilateral ptosis, limited eye movements, lower extremities paresthesias, and unsteadiness, Multiple mtDNA deletions detected by PCR in muscle
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 31, Age of Patient: 34, Age of Death: n/a

Reference:	Wolf et al, 2009; [PubMed] 16
Description:	Developemental delay, status epilepticus onset, valproic acid therapy 2 weeks, epilepsia partialis continua, mtDNA depletion in liver
Mutations:	A467T, A467T
Age group:	infantile
Age of Onset: 2.67, Age of Patient: 6, Age of Death: n/a

Reference:	Wolf et al, 2009; [PubMed] 17
Description:	status epilepticus onset, valproic acid therapy 12 weeks, liver failure,
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 9.25, Age of Patient: 11, Age of Death: n/a

Reference:	McHugh et al, 2010; [PubMed] 18
Description:	progressive difficulty walking, hand and foot numbness, ataxia, dysarthria, ptosis, sensory ataxia, with progressive ophthalmoplegia, dysarthria, nystagmus, dysphagia. Dysarthria became evident from age 55 years, and she developed ptosis at 62 years.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 42, Age of Patient: 62, Age of Death: n/a

Reference:	McHugh et al, 2010; [PubMed] 19
Description:	progressive imbalance, hand and foot numbness, with impotence and dysarthria, progressive diplopia, bilateral ptosis with severe ophthalmoparesis in all directions and diplopia on lateral gaze. There was mild dysarthria and severe sensory ataxia, mild weakness in proximal and distal muscle groups, myopathy, multiple mtDNA deletions in muscle.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 41, Age of Patient: 46, Age of Death: n/a

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Reference:	Brinjikji et al, 2011; [PubMed] 20
Description:	Elevated CSF protein, occipital stroke, visual field deficit, peripheral neuropathy, migraine, epilepsy, ataxia, myoclonus, progressive gait ataxia, ophthalmoplegia, dysarthria, dysphagia, valproate induced encephalopathy and depression
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 18, Age of Patient: 39, Age of Death: n/a

Reference:	Brinjikji et al, 2011; [PubMed] 21
Description:	Hospitalized at age 7 for headache, fever, lethargy, and seizures, Elevated CSF protein, occipital stroke, visual field deficit, peripheral neuropathy, migraine, epilepsy, The patient began valproate therapy at age 11 and suffered hepatic encephalopathy which resolved after carnitine therapy.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 7, Age of Patient: 28, Age of Death: n/a

Reference:	Hunter et al, 2011; [PubMed] 22
Description:	Myoclonic Seizures, Focal motor seizures, Epilepsia partialis continua, Developmental Delay or Regression, Abnormal Liver Enzymes, Alpers
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 5, Age of Patient: n/a, Age of Death: 10.83

Reference:	Visser et al, 2011; [PubMed] 23
Description:	Migraine, seizures, dysphasia, magnesium infusion stopped the seizures
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 17, Age of Patient: n/a, Age of Death: n/a

Reference:	Visser et al, 2011; [PubMed] 24
Description:	Seizures, magnesium infusion stopped the seizures
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 19, Age of Patient: n/a, Age of Death: n/a

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Reference:	Tang et al, 2012; [PubMed] 25
Description:	ptosis, PEO, muscle weakness, fatigability, peripheral neuropathy, ataxia, lactic acidosis and diarrhea alternating with constipation, ragged-red fibers,
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: n/a, Age of Patient: 46, Age of Death: n/a

Reference:	Lax et al, 2012a; [PubMed] 26
Description:	CPEO, Ptosis, Peripheral neuropathy, COX-deficient fibers, presence of mitochondrial dna deletions in muscle, Severe sensory and moderate motor neuronopathy, Distal and proximal neurogenic change,
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 41, Age of Patient: 44, Age of Death: n/a

Reference:	Lax et al, 2012a; [PubMed] 27
Description:	CPEO, Ptosis, Peripheral neuropathy, COX-deficient fibers, ragged red fibers, presence of mitochondrial dna deletions in muscle, Sensory and motor neuronopathy, Distal neurogenic change, proximal myopathy.
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 18, Age of Patient: 36, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 28
Description:	Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, myoclonus, neuropathy
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 15, Age of Patient: 20, Age of Death: n/a

Reference:	Boes et al, 2009; [PubMed] 29
Description:	Presented with status epilepticus, cerebellar ataxia and myoclonus, epilepsia partialis continua, Transient liver dysfunction with sodium valproate treatment at age 15, refractory focal motor status at age 17,
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 5, Age of Patient: n/a, Age of Death: 17

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Reference:	Tzoulis et al, 2013; [PubMed] 30
Description:	Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 16, Age of Patient: n/a, Age of Death: 53

Reference:	Tzoulis et al, 2013; [PubMed] 31
Description:	Epilepsy, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 15, Age of Patient: 42, Age of Death: n/a

Reference:	Hanisch et al, 2014; [PubMed] 32
Description:	Ataxia, ptosis, pareses, sensory neuropathy, motor neuropathy, axonal neuropathy
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 38, Age of Patient: 40, Age of Death: n/a

Reference:	Tzoulis et al, 2014; [PubMed] 33
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 8, Age of Patient: n/a, Age of Death: 47

Reference:	Tzoulis et al, 2014; [PubMed] 34
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 15, Age of Patient: n/a, Age of Death: 44

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Reference:	Tzoulis et al, 2014; [PubMed] 35
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 16, Age of Patient: n/a, Age of Death: 53

Reference:	Schicks et al, 2010; [PubMed] 36
Description:	early-onset ataxia, epilepsy, sensory neuropathy.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 12.5, Age of Patient: n/a, Age of Death: n/a

Reference:	Van Goethem et al, 2004; [PubMed] 37
Description:	Increasing gait unsteadiness, mild cognitive decline in the fifth decade. Cataracts. ataxic gait. Deep tendon reflexes were absent. Vibration and position sense were absent at the lower limbs early on, whereas light touch sensation was decreased at a later stage. Pes Cavus. gaze paresis, nystagmus. axonal generalized peripheral neuropathy. brainstem dysfunction.
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: n/a, Age of Patient: 49, Age of Death: n/a

Reference:	Van Goethem et al, 2004; [PubMed] 38
Description:	Increasing gait unsteadiness. ataxic gait. Deep tendon reflexes were absent. Vibration and position sense were absent at the lower limbs early on, whereas light touch sensation was decreased at a later stage. Pes Cavus. Dysarthria. horizontal and vertical gaze-evoked nystagmus. axonal generalized peripheral neuropathy. brainstem dysfunction.
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: n/a, Age of Patient: 47, Age of Death: n/a

Reference:	Van Goethem et al, 2004; [PubMed] 39
Description:	at 18 year of age, he hadstatus epilepticus lasting 8 days, followed by a “Todd paralysis” of the left arm and face. Five years later, he had an acute psychiatric illness, hyperventilation, gastrointestinal symptoms, gait unsteadiness, and disturbed limb coordination. Between 32 and 35 years of age, he lost 13 kg of weight. On exami- nation, he had sensory gait ataxia, limb ataxia, areflexia, generalized dystrophy, and loss of vibration and static joint position sense at the distal lower limbs, severe dysarthria, and a left-sided Babinski sign. Romberg test was positive. intestinal pseudo-obstruction, anorexia, and further weight loss. A few weeks later, he developed stupor (Glasgow coma scale, 5/15), hyperventilation, myoclonic jerks, and seizures necessitating intensive care and artificial ventilation. gastroparesis. dilated cardiomyopathy.
Mutations:	A467T, A467T
Age group:	juvenile
Age of Onset: 18, Age of Patient: n/a, Age of Death: 39

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Reference:	Rajakulendran et al, 2016; [PubMed] 40
Description:	Alpers. Speech and motor delay were noted at the age of two years. At three years she developed epilepsy and six months later experienced migrainous attacks associated with vomiting, vertigo and transient left-sided weakness. At the age of five years she developed status epilepticus. A month later she was noted to have nystagmus, hypotonia of the lower limbs and absent knee jerks. Liver dysfunction.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 3, Age of Patient: n/a, Age of Death: 5.5

Reference:	Rajakulendran et al, 2016; [PubMed] 41
Description:	MELAS. Occipital headaches. left homonymous hemianopia suggestive of a stroke-like episode. right occipital infarct. Jerking movements of her left arm suggestive of epilepsia partialis continua with dystonia, which was refractory to treatment. She developed an asymptomatic axonal neuropathy, deafness and myopathic weakness. bilateral ptosis, ophthalmoparesis, a dense left homonymous hemianopia, dysarthric speech, increased tone with clawing of the left hand, and distal muscle weakness. In addition, Romberg’s test was positive and she walked with a wide-based gait. ataxic gait. axonal sensory motor neuropathy. ragged red fibres and COX-negative fibres.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 24, Age of Patient: 31, Age of Death: n/a

Reference:	Rajakulendran et al, 2016; [PubMed] 42
Description:	MEMSA. sensory neuropathy affecting legs. normal development until the age of 6 years when she presented with an encephalopathic illness consisting of impaired consciousness, vomiting and generalised tonic-clonic seizures. One week later she developed a left homonymous hemianopia. She remained stable until the age of 13 years when she developed stimulus sensitive myoclonus, tremor and a progressive cerebellar ataxia. Mildly elevated blood lactate and alanine levels and a sensory axonal peripheral neuropathy. occipital lobe infarcts. COX negative fibres. gaze-evoked nystagmus at 17. hand tremor, stimulus- sensitive myoclonus, head titubation, and gait ataxia.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 6, Age of Patient: 16, Age of Death: n/a

Reference:	Rajakulendran et al, 2016; [PubMed] 43
Description:	SANDO. Severe axonal neuropathy. COX-negative fibres, ragged red fibres. presented at the age of 20 years with diplopia and bilateral ptosis. Over the next five years he developed dysphagia, slurred speech and an unsteady gait. tingling sensation in hands, feet, leg, trunk and arms. at 44 years demonstrated bilateral ptosis and limitation of eye movements in all directions of gaze. dysarthria. Romberg’s test was positive. ataxic gait. axonal sensory peripheral neuropathy. ragged red fibres and more than 10 COX-negative fibres.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 20, Age of Patient: 44, Age of Death: n/a

Reference:	Janssen et al, 2016; [PubMed] 44
Description:	At 21 years, presented with a first generalized tonic–clonic seizure. She complained of migraine afterward and developed a convulsive status epilepticus. Visual hallucinations, jerking of the right arm with secondary generalization. She died 7 months after initial presentation.
Mutations:	A467T, A467T
Age group:	adult
Age of Onset: 21, Age of Patient: 21, Age of Death: 21.6

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Reference:	Janssen et al, 2016; [PubMed] 45
Description:	Sudden falls, frequent negative myoclonus, ataxic gait and loss of proprioception in the distal extremities with nerve conduction studies demonstrating a mild axonal sensory polyneuropathy. myoclonic status epilepticus, generalized tonic–clonic seizure.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 12, Age of Patient: 18, Age of Death: 27

Reference:	Simonati et al, 2003a; [PubMed] 46
Description:	During his early childhood, he had frequent “acetonaemic vomiting” and stunted growth. At age 7 years, he developed EPC and sensory ataxia. epilepsia partialis continua, followed by progressive ataxia Reduced density of the white matter. behavioural problems. Elevated blood lactate. myoclonic seizures. sensory ataxia, absent deep tendon reflexes, cerebellar dysfunction, nystagmus, peripheral vision defect, and a pale optic disk. mild atrophy of the frontal,parietal and visual cortices, focal hyperlucencies of the frontal and occipital cortex, as well as of the thalamus bilaterally, and cerebellar atrophy. COX-negative fibres. partial and generalized seizures as well as myoclonic fits.
Mutations:	A467T, A467T
Age group:	childhood
Age of Onset: 7, Age of Patient: 18, Age of Death: 19

Reference:	Blok et al, 2009; [PubMed] 47
Description:	MELAS-like, features including occipital lobe epilepsy.
Mutations:	A467T, W748S
Age group:	juvenile
Age of Onset: n/a, Age of Patient: 19, Age of Death: n/a

Reference:	Blok et al, 2009; [PubMed] 48
Description:	Occipital lobe epilepsy, myoclonus, cognitive delay, polyneuropathy, cerebellar ataxia.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: n/a, Age of Patient: 40, Age of Death: n/a

Reference:	Blok et al, 2009; [PubMed] 49
Description:	Ptosis, CPEO, polyneuropathy, cerebellar ataxia, dysarthria.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: n/a, Age of Patient: 47, Age of Death: n/a

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Reference:	Horvath et al, 2006; [PubMed] 50
Description:	Onset at 34 years with PEO, ataxia, dysphagia, myopathy, neuropathy and Diabetes.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 34, Age of Patient: n/a, Age of Death: n/a

Reference:	Kollberg et al, 2006; [PubMed] 51
Description:	Started as an ataxic syndrome, Alpers, ragged red fibers, COX-deficient fibers, mtDNA deletions. mtDNA copy numbers 1.6 fold. She was healthy and developed normally until her late preschool years when she developed slowly progressive ataxia. Occasional myoclonic seizures, and at 13 years of age, valproate treatment was started because of occipital seizures. ataxia, dementia, and cortical blindness. She developed refractory seizures, including multifocal EPC, status epilepticus, and myoclonus.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	childhood
Age of Onset: 5, Age of Patient: 13, Age of Death: 14

Reference:	Kollberg et al, 2006; [PubMed] 52
Description:	psychomotor regression, refractory seizures, stroke-like episodes, hepatopathy, and ataxia. COX-deficient muscle fibers, mtDNA deletions, 160% mtDNA copy number. He was normal until 11 years of age when he developed mild tremor and ataxia. At 13 years of age, he reported occasional migraine-like headaches and was found to have mild ataxia and myoclonus. generalized seizures. mild leftsided hemiparesis, external ophthalmoplegia, and peripheral neuropathy.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	childhood
Age of Onset: 11, Age of Patient: 24, Age of Death: n/a

Reference:	Sarzi et al, 2007; [PubMed] 53
Description:	Feeding difficulties 2 days after birth and trunk hypotonia, dysmorphy, hypotonia, coloboma, heart failure at 2 months, liver insufficiency at 4 months. Liver and muscle mtDNA depletion.
Mutations:	A467T, K561M, W748S
Age group:	infantile
Age of Onset: 0.001, Age of Patient: n/a, Age of Death: 0.5

Reference:	Schulte et al, 2009; [PubMed] 54
Description:	Dysarthria, sensory neuropathy, PEO, minor cognitive dysfunction, depression.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 34, Age of Patient: n/a, Age of Death: n/a

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Reference:	Stewart et al, 2009; [PubMed] 55
Description:	PEO, ataxia, seizures, ptosis, bilateral deafness, myopathy, dysarthria, peripheral neuropathy, multiple mtDNA deletions. 5% COX deficient fibers, 2% RRF.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 39, Age of Patient: n/a, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 56
Description:	Autistic features, headaches/migraines, ataxia, seizures, intractable seizure, optic atrophy, abnormal MRI, dystonia, posterior stroke, abnormal EEG. 101% mtDNA copy number in blood.
Mutations:	A467T, W748S
Age group:	juvenile
Age of Onset: n/a, Age of Patient: 18, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 57
Description:	Hearing loss, Ataxia Neuropathy Spectrum, Seizures, dementia, developmental delay
Mutations:	A467T, Q497H, W748S
SNPs:	E1143G
Age group:	juvenile
Age of Onset: 17, Age of Patient: n/a, Age of Death: n/a

Reference:	Hansen et al, 2012; [PubMed] 58
Description:	gait instability, manual coordination disorder, speech disturbance and secondary generalized motor seizures, tension-type headaches, complete external ophthalmoplegia, cerebellar dysarthria and ataxia, sensory ataxia in Romberg-testing, areflexia of the lower extremities, mild cognitive dysfunction, epileptic seizures, generalised cortical atrophy, sensory axonal neuropathy, dysarthria
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 23, Age of Patient: 48, Age of Death: n/a

Reference:	Kinghorn et al, 2012; [PubMed] 59
Description:	Ataxia, dysarthria, suffered two generalized seizures, and developed severe progressive cognitive decline and psychiatric manifestations including visual and auditory hallucinations, bilateral external ophthalmoplegia, bilateral ptosis, and reduced visual acuities, bilateral sensorineural hearing loss, proximal muscle weakness in all four limbs and was areflexic, severe sensory neuropathy and myopathy,
Mutations:	A467T, W748S
Age group:	juvenile
Age of Onset: n/a, Age of Patient: 18, Age of Death: 65

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Reference:	Kinghorn et al, 2012; [PubMed] 60
Description:	Diplopia, partial ophthalmoparesis in all directions of gaze and dysarthria, sensory neuropathy, COX-deficient fibers, multiple mtDNA deletions,
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: n/a, Age of Patient: 50, Age of Death: n/a

Reference:	Pelayo-Negro et al, 2012; [PubMed] 61
Description:	ataxia, sensory neuropathy, dysarthria, and external ophthalmoparesis
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 30, Age of Patient: 50, Age of Death: n/a

Reference:	Lax et al, 2012a; [PubMed] 62
Description:	CPEO, Ptosis, Peripheral neuropathy, COX-deficient fibers, presence of mitochondrial dna deletions in muscle, ataxia, Severe sensory, moderate motor axonal neuronopathy, Distal neurogenic, proximal myopathy
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 41, Age of Patient: 48, Age of Death: n/a

Reference:	Lax et al, 2012a; [PubMed] 63
Description:	CPEO, Ptosis, Peripheral neuropathy, COX-deficient fibers, ragged red fibers, presence of mitochondrial dna deletions in muscle, Severe sensory and moderate motor neuronopathy, Distal neurogenic change, proximal myopathy
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 34, Age of Patient: 47, Age of Death: n/a

Reference:	Lax et al, 2012a; [PubMed] 64
Description:	Peripheral neuropathy, ataxia, epilepsy, COX-deficient fibers, presence of mitochondrial dna deletions in muscle, Moderate sensory neuronopathy
Mutations:	A467T, W748S
Age group:	juvenile
Age of Onset: 16, Age of Patient: 18, Age of Death: n/a

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Reference:	Lax et al, 2012a; [PubMed] 65
Description:	Peripheral neuropathy, ataxia, epilepsy, presence of mitochondrial dna deletions in muscle,
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 20, Age of Patient: 24, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 66
Description:	Presented with epilepsy and headaches, ataxia, status epilepticus, nystagmus, myoclonus, neuropathy. Sodium valproate treatment 6 weeks prior to death. Liver dysfunction, cause of death status epilepticus and liver failure. Hepatic histology showed acute liver necrosis.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	juvenile
Age of Onset: 19, Age of Patient: n/a, Age of Death: 19

Reference:	Tzoulis et al, 2006; [PubMed] 67
Description:	Presented with epilepsy and headaches, ataxia, epilepsy, status epilepticus, myoclonus, neuropathy. Sodium valproate treatment 7 weeks prior to death. Liver dysfunction and rising liver enzymes and bilirubin terminally, cause of death status epilepticus. Hepatic histology showed centrolobular degeneration.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	juvenile
Age of Onset: 14, Age of Patient: n/a, Age of Death: 23

Reference:	Tzoulis et al, 2006; [PubMed] 68
Description:	Presented with epilepsy, ataxia, status epilepticus, headaches, myoclonus, neuropathy. Sodium valproate treatment for 8 months. Stopped just prior to death. Liver dysfunction, cause of death liver failure. Hepatic histology showed acute liver necrosis.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	childhood
Age of Onset: 10, Age of Patient: n/a, Age of Death: 10

Reference:	Tzoulis et al, 2006; [PubMed] 69
Description:	Presented with epilepsy, headaches, epilepsy, status epilepticus, headaches, nystagmus, and neuropathy. Sodium valproate treatment for 2 months then stopped 2 months prior to death. Liver dysfunction, liver transplant 1 month prior to death, cause of death liver failure. Hepatic histology showed acute liver necrosis.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: 20, Age of Patient: n/a, Age of Death: 20

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Reference:	Tzoulis et al, 2006; [PubMed] 70
Description:	Presented with epilepsy, status epilepticus, headaches, nystagmus, myoclonus, neuropathy. Sodium valproate treatment 7 weeks prior to death. Liver dysfunction and rising liver enzymes and bilirubin terminally, cause of death status epilepticus. Hepatic histology showed centrolobular degeneration.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	juvenile
Age of Onset: 15, Age of Patient: n/a, Age of Death: 21

Reference:	Tzoulis et al, 2006; [PubMed] 71
Description:	Presented with progressive gait unsteadiness, ataxia, headaches, myoclonus, neuropathy, PEO, ptosis onset at age 44
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: 36, Age of Patient: 50, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 72
Description:	Presented with progressive gait unsteadiness, ataxia, headaches, neuropathy, PEO ptosis onset age 25
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: 24, Age of Patient: 43, Age of Death: n/a

Reference:	Paus et al, 2008; [PubMed] 73
Description:	Presented with PEO, mild bilateral ptosis, dysarthria, ataxia, and neuropathy
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: 36, Age of Patient: 37, Age of Death: n/a

Reference:	Paus et al, 2008; [PubMed] 74
Description:	episodic headache, cognitive decline, and seizures, repeatedly resulting in generalized status epilepticus, ataxia, sensorimotor peripheral neuropathy, dysarthria, PEO with diplopia, mild bilateral ptosis, epilepsy, cognitive impairment, myoclonus,
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 28, Age of Patient: 39, Age of Death: n/a

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Reference:	Rouzier et al, 2013; [PubMed] 75
Description:	R-EPC (refractory epilepsia partialis continua), axonal neuropathy, cerebellar ataxia, hyperintensity of rolandic, occipital and cerebellar cortex and dentate nucleus.
Mutations:	A467T, W748S
Age group:	juvenile
Age of Onset: 17, Age of Patient: n/a, Age of Death: n/a

Reference:	Posada et al, 2010; [PubMed] 76
Description:	Ataxic sensory neuropathy, dysarthria, progressive ophthalmoplegia, paresthesia of lower extremities, unsteady gait, slurred speech, absent deep tendon reflexes, vibrations, ataxic gait and positive Romberg sign. Multiple mtDNA deletions, a marked decrease in mtDNA copy number.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: 37, Age of Patient: 47, Age of Death: n/a

Reference:	Roshal et al, 2011; [PubMed] 77
Description:	Focal parieto-occipital lobe seizures, migraine headaches, cerebellar ataxia, sensory–motor axonal neuropathy, and impairment of visual perception and cognitive function.
Mutations:	A467T, W748S
Age group:	juvenile
Age of Onset: 15, Age of Patient: 16, Age of Death: n/a

Reference:	Tuladhar et al, 2013; [PubMed] 78
Description:	abnormal gait, ataxia, PEO, and jerky torticollis, mild cerebellar atrophy, sensory neuronopathy.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 43, Age of Patient: 45, Age of Death: n/a

Reference:	Tzoulis et al, 2013; [PubMed] 79
Description:	Ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 24, Age of Patient: 50, Age of Death: n/a

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Reference:	Tzoulis et al, 2013; [PubMed] 80
Description:	Ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 36, Age of Patient: 58, Age of Death: n/a

Reference:	Hanisch et al, 2014; [PubMed] 81
Description:	Ataxia, ptosis, mild cognitive impairment, sensory neuropathy, motor neuropathy, axonal neuropathy, demyelinating neuropathy.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 41, Age of Patient: 45, Age of Death: n/a

Reference:	Hanisch et al, 2014; [PubMed] 82
Description:	Ataxia, ptosis, pareses, diabetes, sensory neuropathy, motor neuropathy, axonal neuropathy, demyelinating neuropathy.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 49, Age of Patient: 56, Age of Death: n/a

Reference:	Lax et al, 2012b; [PubMed] 83
Description:	Ataxia, Epilepsy, Dementia, Encephalopathy, Myoclonus, Fatigue, Depression, Dysarthria, Cardiac failure, cardiomyopathy, Diabetes, arPEO, Ischemic heart disease.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 20, Age of Patient: 24, Age of Death: n/a

Reference:	Sitarz et al, 2014; [PubMed] 84
Description:	Ataxia, neuropathy, PEO, MIRAS.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: n/a, Age of Patient: 39, Age of Death: n/a

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Reference:	Tzoulis et al, 2014; [PubMed] 85
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy.
Mutations:	A467T, W748S
Age group:	juvenile
Age of Onset: 13, Age of Patient: n/a, Age of Death: 21

Reference:	Tzoulis et al, 2014; [PubMed] 86
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy.
Mutations:	A467T, W748S
Age group:	juvenile
Age of Onset: 14, Age of Patient: n/a, Age of Death: 23

Reference:	Van Goethem et al, 2004; [PubMed] 87
Description:	minor tremor of the hands from age 12 years. In his late 20s, he experienced tingling in both hands, followed by tingling in the legs. In the early fourth decade, he became unsteady at walking, especially in the dark. From his early 40s, his speech became slurred (dysarthria). On examination at age 52 years, he had an ataxic gait, and Romberg test was positive. There was dysarthria and bilateral ophthalmoparesis. generalized areflexia.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	childhood
Age of Onset: 12, Age of Patient: 52, Age of Death: n/a

Reference:	Janssen et al, 2016; [PubMed] 88
Description:	Migraine, ataxia, polyneuropathy. focal seizures with visual symptoms and motor signs, and secondary generalized tonic-clonic seizure. Clinical neurological examination revealed an ataxic gait and areflexia with sensory loss. Convulsive status epilepticus. Cerebral MRI revealed a left occipital and left thalamic lesion.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	juvenile
Age of Onset: 17, Age of Patient: 20, Age of Death: 23

Reference:	Janssen et al, 2016; [PubMed] 89
Description:	Presented with status epilepticus, occipital lobe seizures. Further neurologic examination showed ataxic gait and appendicular ataxia. chronic sensory axonal polyneuropathy. Cognitive decline. At follow-up consultation 6 months after the initial presentation, she had not experienced any more seizures.
Mutations:	A467T, W748S
SNPs:	E1143G
Age group:	juvenile
Age of Onset: 18, Age of Patient: 18.7, Age of Death: n/a

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Reference:	Janssen et al, 2016; [PubMed] 90
Description:	She had occipital lobe and secondarily generalized seizures. In addition, she had PEO, truncal and appendicular ataxia and peripheral neuropathy with diminished vibration sense and areflexia. She reported sporadic occurrence of seizures with a frequency of once in every few months.
Mutations:	A467T, W748S
Age group:	adult
Age of Onset: 21, Age of Patient: 47, Age of Death: n/a

Reference:	Ashley et al, 2008; [PubMed] 91
Description:	Hepatopathy, Epilepsy, Hepatopathy,
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 1.5, Age of Patient: n/a, Age of Death: n/a

Reference:	de Vries et al, 2007; [PubMed] 92
Description:	Onset at 6 months with FTT, dementia, hypotonia, seizures, hepatopathy, aplasia cutis, delayed myelinisation. Death at 15 months.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 1.3

Reference:	Ferrari et al, 2005; [PubMed] 93
Description:	He developed normally in the first 6 months. Refusal of food and failure to thrive were noted from the 7th month of life. At 1 year of age, increased transaminase levels in the blood were accompanied by liver enlargement and hyperecogenicity. Motor development was delayed. hypoglycaemic episodes and lactic acidosis. A liver biopsy at the age of 16 months revealed steatosis and fibrosis. At 20 months of age, he had numerous episodes of status epilepticus and epilepsia partialis continua. The patient died at 2.5 years of age during an episode of status epilepticus. Alpers’ syndrome.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 2.5

Reference:	Kollberg et al, 2006; [PubMed] 94
Description:	Ragged Red Fibers, COX-Deficient Fibers. The boy had feeding difficulties with failure to thrive since 3 months of age. Delayed motor development. general muscle weakness and ataxia. compromised liver function.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.33, Age of Patient: n/a, Age of Death: 1.33

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Reference:	Stewart et al, 2009; [PubMed] 95
Description:	Alpers, Epilepsy, developmental delay, COX deficient fibres.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a

Reference:	Stewart et al, 2009; [PubMed] 96
Description:	Alpers, seizures, developmental delay, liver failure, hypotonia, impaired vision, renal stones, mtDNA depletion in muscle. 5% COX deficient fibers.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.7, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 97
Description:	Developmental delay, dementia, seizures, Alpers
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 2, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 98
Description:	Developmental delay, dementia, seizures, Alpers, Ataxia
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 2, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 99
Description:	Developmental delay, dementia, seizures, Alpers, Lactic acidosis, Cortical athrophy, hypoglycemia
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 1.5, Age of Patient: n/a, Age of Death: n/a

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Reference:	Wong et al, 2008; [PubMed] 100
Description:	Developmental delay, dementia, seizures, Alpers, Lactic acidosis, Stroke
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 2, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 101
Description:	Developmental delay, dementia, seizures, Alpers, Stroke, ataxia, exercise intolerance
Mutations:	A467T, G848S
Age group:	childhood
Age of Onset: 9, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 102
Description:	Developmental delay, dementia, seizures, Alpers, hypotonia, failure to thrive
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.8, Age of Patient: n/a, Age of Death: n/a

Reference:	Nguyen et al, 2005; [PubMed] 103
Description:	Refractory seizures, psychomotor regression, liver disease, Transient hypoglycemia, Transient lactic academia, Elevated CSF protein, presented with epilepsia partialis continua,
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.9, Age of Patient: n/a, Age of Death: 1.8

Reference:	Nguyen et al, 2005; [PubMed] 104
Description:	Refractory seizures, psychomotor regression, liver disease, presented with liver failure
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 1, Age of Patient: n/a, Age of Death: 1.3

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Reference:	Saneto et al, 2010; [PubMed] 105
Description:	Cyclic vomiting, episodic hypoglycemia then seizure onset at 6 years, generalized seizures, GI dysmotility, eyelid ptosis,ophthalmoplegia, sensorineural hearning loss, absent smooth pursuit eye movements
Mutations:	A467T, G848S
Age group:	childhood
Age of Onset: 6, Age of Patient: 11, Age of Death: n/a

Reference:	Hunter et al, 2011; [PubMed] 106
Description:	Myoclonic Seizures, Epilepsia partialis continua, Developmental Delay or Regression, ataxia, Abnormal Liver Enzymes, Serum Lactate, liver mtDNA depletion, Alpers
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 3.33

Reference:	Hunter et al, 2011; [PubMed] 107
Description:	Myoclonic Seizures, Generalized tonic-clonic seizures, Focal motor seizures, Developmental Delay or Regression, hypotonia, tremor, Abnormal Liver Enzymes, Serum Lactate, liver mtDNA depletion, death by liver failure, Alpers
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.83, Age of Patient: n/a, Age of Death: 0.92

Reference:	McCoy et al, 2011; [PubMed] 108
Description:	focal seizures, elevated liver transaminases, Elevated CSF protein, patient died several weeks later
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.8, Age of Patient: n/a, Age of Death: 1

Reference:	Scalais et al, 2012; [PubMed] 109
Description:	presented with hypoglycemia, lactic acidosis, moderate ketosis and liver dysfunction, generalized hypotonia, progressive jaundice and abdominal distension with ascites, status epilepticus with generalized tonico-clonic seizures. She had an intermittent tremor, moderate truncal ataxia with a wide-based gait, myoclonic seizures, epilepsia partialis continua,
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.29, Age of Patient: n/a, Age of Death: 5

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Reference:	de Vries et al, 2008; [PubMed] 110
Description:	Delayed motor and mental development, From the age of 3 years his psychomotor development declined and epilepsy, visual impairment and sensorineuronal deafness, epilepsia partialis continua. Bilateral ptosis, generalized hypotonia, ataxia, absent reflexes and hyperlaxity by age 5.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 3, Age of Patient: 5, Age of Death: n/a

Reference:	Hasselmann et al, 2010; [PubMed] 111
Description:	Alpers, status epilepticus and somnolence, ataxia with dysmetria and muscular hypotonia. Healthy unrelated parents. Laboratory investigations revealed myoclonic epilepsy with ragged red fibers,
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 2.2, Age of Patient: 3.5, Age of Death: 5.5

Reference:	Tzoulis et al, 2013; [PubMed] 112
Description:	Epilepsy, stroke-like episodes.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.6, Age of Patient: n/a, Age of Death: 0.6

Reference:	Roels et al, 2009; [PubMed] 113
Description:	mtDNA depletion. severe hypoglycemia, liver biopsy shows micronodular cirrhosis. At 3 y 9 m, status epilepticus develops which occurs again at 4 y and is difficult to control. myoclonia. She dies from bronchopulmonary infection when 5 y old. COX negative fibers.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.25, Age of Patient: 4, Age of Death: 5

Reference:	Tzoulis et al, 2014; [PubMed] 114
Description:	Epilepsy, stroke-like episode.
Mutations:	A467T, G848S
Age group:	infantile
Age of Onset: 0.6, Age of Patient: n/a, Age of Death: 0.6

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Reference:	Ashley et al, 2008; [PubMed] 115
Description:	Epilepsy, hepatopathy, movement disorder (present but not prominent)
Mutations:	A467T
SNPs:	PNF
Age group:	infantile
Age of Onset: 0.33, Age of Patient: n/a, Age of Death: n/a

Reference:	Ashley et al, 2008; [PubMed] 116
Description:	Epilepsy, hepatopathy, movement disorder (present but not prominent)
Mutations:	A467T
SNPs:	PNF
Age group:	infantile
Age of Onset: 0.58, Age of Patient: n/a, Age of Death: n/a

Reference:	Ashley et al, 2008; [PubMed] 117
Description:	mtDNA depletion (30% in muscle), epilepsy, hepatopathy, movement disorder
Mutations:	A467T, PNF
Age group:	infantile
Age of Onset: 1.5, Age of Patient: n/a, Age of Death: n/a

Reference:	Sarzi et al, 2007; [PubMed] 118
Description:	Myoclonus epilepsy, Epilepsy, Alpers syndrome, steatosis, death at 3 years
Mutations:	A467T
SNPs:	PNF
Age group:	childhood
Age of Onset: 3, Age of Patient: n/a, Age of Death: 3

Reference:	Sarzi et al, 2007; [PubMed] 119
Description:	Seizures, Alpers syndrome, Jaundice at 9 months and liver enlargement.
Mutations:	A467T
SNPs:	PNF
Age group:	infantile
Age of Onset: 0.66, Age of Patient: n/a, Age of Death: n/a

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Reference:	Wong et al, 2008; [PubMed] 120
Description:	Alpers, stroke, hypotonia, Dementia, developmental delay, seizures.
Mutations:	A467T
SNPs:	PNF
Age group:	infantile
Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 121
Description:	Developmental delay, dementia, seizures, Alpers
Mutations:	A467T
SNPs:	PNF
Age group:	childhood
Age of Onset: 4, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 122
Description:	Developmental delay, dementia, seizures, Alpers, Family history of acute liver failure
Mutations:	A467T
SNPs:	PNF
Age group:	infantile
Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 123
Description:	Developmental delay, dementia, seizures, Alpers, Ptosis, ataxia, visual hallucinations
Mutations:	A467T
SNPs:	PNF
Age group:	childhood
Age of Onset: 3, Age of Patient: n/a, Age of Death: n/a