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:	Blok et al, 2009; [PubMed] 1
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

Reference:	Kollberg et al, 2006; [PubMed] 2
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] 3
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] 4
Description:	Onset with walking difficulties, seizures at 2.5 years, hepatocellular insufficiency after valproate treatment, alpers syndrome, Liver mtDNA depletion.
Mutations:	W748S
SNPs:	E1143G
Age group:	infantile
Age of Onset: 2, Age of Patient: n/a, Age of Death: 3

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Reference:	Tzoulis et al, 2006; [PubMed] 5
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] 6
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] 7
Description:	Presented with epilepsy, ataxia, nystagmus, neuropathy, ptosis/ PEO onset at age 65
Mutations:	W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: 55, Age of Patient: 74, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 8
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] 9
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] 10
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] 11
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] 12
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] 13
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:	Amiot et al, 2009; [PubMed] 14
Description:	Peripheral neuropathy, PEO, ataxia, hearing loss, dysarthria-dysphonia, urinary tract involvement
Mutations:	A143V, W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: 40, Age of Patient: 49, Age of Death: n/a

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Reference:	Palin et al, 2012; [PubMed] 15
Description:	No neurological symptoms, but type-2 diabetes and hypertension.
Mutations:	W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: n/a, Age of Patient: 63, Age of Death: n/a

Reference:	Posada et al, 2010; [PubMed] 16
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:	Van Goethem et al, 2004; [PubMed] 17
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] 18
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] 19
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:	Ashley et al, 2008; [PubMed] 20
Description:	reported as Alpers, onset at 16 years, presenting encephalopathy with epilepsy, hepatopathy, and movement disorder (ataxia). 108% mtDNA copy number in muscle.
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 16, Age of Patient: n/a, Age of Death: n/a

Reference:	Schulte et al, 2009; [PubMed] 21
Description:	cerebellar ataxia, dysarthria/dysphagia, sensory neuropathy, PEO, epilepsy, moderate cerebellar atrophy.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: 22, Age of Patient: n/a, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 22
Description:	Ataxia, peripheral neuropathy, exercise intolerance, easy fatigueability, cerebellar atrophy, abnormal MRI. 82% mtDNA copy number in blood.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: n/a, Age of Patient: 30, Age of Death: n/a

Reference:	Tang et al, 2011; [PubMed] 23
Description:	Headaches/migraines, ataxia, peripheral neuropathy, exercise intolerance, ophthalmoporesis/CPEO, abnormal EMG/NCV, ptosis, constipation, pseudo-obstruction, hearing loss, abnormal BAERS. 83% mtDNA copy number in blood.
Mutations:	W748S, W748S
SNPs:	S28C
Age group:	adult
Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a

Reference:	Winterthun et al, 2005; [PubMed] 24
Description:	Ataxia, sensory ataxia, dysarthria, nystagmus, cognitive dysfunction, axonal neuropathy, demyelinating neuropathy. This man presented at age 26 with unsteadiness. Examination showed an ataxic gait, cerebellar dysarthria, myoclonic jerks of his head and facial muscles, mild limitation of horizontal eye movement, and horizontal nystagmus in the direction of gaze, with an additional vertical element when looking down. There were distal amyotrophy, absent reflexes in the legs, and a symmetric loss of all sensory modalities below the knee. Romberg’s test was positive. Episodes of depression. At age 31 he has an almost complete ophthalmoplegia, cerebellar dysarthria, myoclonus involving face and arms, truncal ataxia, and symmetric dysmetria.
Mutations:	Q497H, Q497H, W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 23, Age of Patient: 38, Age of Death: n/a

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Reference:	Winterthun et al, 2005; [PubMed] 25
Description:	Headaches, a focal epilepsy with secondary generalisation, occipital epilepsy, dysarthria, nystagmus, cognitive dysfunction. Demyelinating neuropathy, axonal neuropathy. headaches preceded by visual symptoms, nausea, vomiting, and unsteadiness diagnosed as migraine. Shortly after, she had the first of a series of tonic-clonic seizures preceded by headache. Examination showed horizontal and vertical nystagmus, gait ataxia.
Mutations:	Q497H, Q497H, W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 15, Age of Patient: 18, Age of Death: n/a

Reference:	Wong et al, 2008; [PubMed] 26
Description:	Onset 33 years with neuropathy, myopathy, SANDO, lactic acidosis, PEO.
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 33, Age of Patient: n/a, Age of Death: n/a

Reference:	Milone et al, 2011; [PubMed] 27
Description:	Stiffness, cramping of the lower extremities, foot numbness, and poor balance. The past medical history was significant for hypogonadotropic hypogonadism diagnosed 10 years prior. ophthalmoplegia without ptosis, mild lower proximal weakness, Multiple mtDNA deletions detected by PCR in muscle
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 32, Age of Patient: 33, Age of Death: n/a

Reference:	Milone et al, 2011; [PubMed] 28
Description:	progressive unsteadiness,limb paresthesias, dysarthria, dysphagia, and weakness, ophthalmoparesis,dysarthria, palatal tremor, moderate axial and appendicular ataxia, and distal pan-modality sensory loss
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 32, Age of Patient: 33, Age of Death: n/a

Reference:	Pelayo-Negro et al, 2012; [PubMed] 29
Description:	ataxia, sensory neuropathy, dysarthria, and external ophthalmoparesis
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: 30, Age of Patient: 51, Age of Death: n/a

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Reference:	Tang et al, 2012; [PubMed] 30
Description:	migraine, ptosis, PEO, exercise intolerance, sensorimotor peripheral neuropathy, ataxia, pseudoobstruction, constipation, and sensorineural hearing loss,
Mutations:	W748S, W748S
SNPs:	S28C
Age group:	adult
Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 31
Description:	Onset with balance disturbances and neuropathy, Gait and limb ataxia, Dysarthria, restricted eye movements, ptosis, Cognitive impairment, Obesity, cramps, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 38, Age of Patient: 44, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 32
Description:	Onset with balance disturbances and neuropathy, Gait and limb ataxia, Myoclonus, tremor, Dysarthria, restricted eye movements, Cognitive impairment, Psychiatric symptoms, Obesity, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 38, Age of Patient: 51, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 33
Description:	Onset with balance disturbances and neuropathy, Gait and limb ataxia, tremor, Involuntary movements, Dysarthria, Dysphagia, Nystagmus, restricted eye movements, Psychiatric symptoms, Muscle strength decreased, Obesity, muscle cramps, amyotrophy, pes cavus, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 27, Age of Patient: 38, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 34
Description:	Onset with balance disturbances, Gait and limb ataxia, Dysarthria, Dysphagia, Nystagmus, diplopia, Cognitive impairment, Muscle strength decreased, sensory neural hearing deficit, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 32, Age of Patient: 46, Age of Death: n/a

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Reference:	Hakonen et al, 2005; [PubMed] 35
Description:	Onset with balance disturbances, Gait and limb ataxia, facial Involuntary movements, Dysarthria, Dysphagia, Nystagmus, other eye-movement abnormalities, Psychiatric symptoms, premature menopause, Obesity, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 27, Age of Patient: 42, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 36
Description:	Onset with epilepsy, Gait and limb ataxia, Epilepsy, Dysarthria, Nystagmus, diplopia, Psychiatric symptoms, Obesity, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 24, Age of Patient: 55, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 37
Description:	Onset with epilepsy, Gait and limb ataxia, Epilepsy, Myoclonus, facial Involuntary movements, Dysarthria, Dysphagia, Nystagmus, other eye-movement abnormalities, Cognitive impairment, Psychiatric symptoms, Muscle strength decreased, Obesity
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 16, Age of Patient: 37, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 38
Description:	Onset with epilepsy, Gait and limb ataxia, Epilepsy, Myoclonus, head tremor, Dysarthria, other eye-movement abnormalities, Nystagmus, Cognitive impairment, Psychiatric symptoms, cramps, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 23, Age of Patient: 45, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 39
Description:	Onset with epilepsy, Gait and limb ataxia, Epilepsy, Myoclonus, head tremor, facial Involuntary movements, Dysarthria, Nystagmus, other eye-movement abnormalities, Cognitive impairment, Psychiatric symptoms, cramps
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 17, Age of Patient: 45, Age of Death: n/a

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Reference:	Hakonen et al, 2005; [PubMed] 40
Description:	Onset with epilepsy, Gait and limb ataxia, Myoclonus, Involuntary movements, Dysarthria, Dysphagia, Nystagmus, other eye-movement abnormalities, Cognitive impairment, Obesity, sensory neural hearing deficit, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 19, Age of Patient: 44, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 41
Description:	Onset with headaches, Gait and limb ataxia, Epilepsy, Myoclonus, Involuntary movements, Dysarthria, Dysphagia, Nystagmus, other eye-movement abnormalities, restricted eye movements, ptosis, Cognitive impairment, Psychiatric symptoms, Muscle strength decreased, Obesity
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 28, Age of Patient: 51, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 42
Description:	Onset with neuropathy, Gait and limb ataxia, Dysarthria, Dysphagia, other eye-movement abnormalities, Cognitive impairment, Psychiatric symptoms, Obesity, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 41, Age of Patient: 58, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 43
Description:	Onset with neuropathy, Gait and limb ataxia, tremor, Dysarthria, Nystagmus, Psychiatric symptoms, Muscle strength decreased, amyotrophy, pes cavus, sensory motor polyneuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 36, Age of Patient: 51, Age of Death: n/a

Reference:	Hakonen et al, 2005; [PubMed] 44
Description:	Onset with tremor, Gait and limb ataxia, Epilepsy, Myoclonus, Involuntary movements, Dysarthria, eye muscle weakness, Cognitive impairment, Psychiatric symptoms, Muscle strength decreased.
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	childhood
Age of Onset: 5, Age of Patient: n/a, Age of Death: 35

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Reference:	Tzoulis et al, 2006; [PubMed] 45
Description:	Presented with epilepsy, ataxia, status epilepticus, headaches, myoclonus, neuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 18, Age of Patient: 19, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 46
Description:	Presented with epilepsy, ataxia, status epilepticus, headaches, myoclonus, neuropathy, ptosis/ PEO onset at age 28. Acute liver failure after 4 months of sodium valproate treatment
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 19, Age of Patient: 33, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 47
Description:	Presented with epilepsy, ataxia, status epilepticus, headaches, nystagmus, myoclonus, neuropathy, treatment with sodium valproate for 2 months, died 3 years later due to status epilepticus, disseminated intravascular coagulation, liver failure.
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	childhood
Age of Onset: 10, Age of Patient: n/a, Age of Death: 22

Reference:	Tzoulis et al, 2006; [PubMed] 48
Description:	Presented with epilepsy, status epilepticus, nystagmus, neuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 17, Age of Patient: 18, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 49
Description:	Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, myoclonus, neuropathy, ptosis/ PEO onset at age 26
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 17, Age of Patient: 38, Age of Death: n/a

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Reference:	Tzoulis et al, 2006; [PubMed] 50
Description:	Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, myoclonus, neuropathy. Sodium valproate treatment 3 months prior to death. Liver dysfunction and rising liver enzymes and bilirubin terminally, cause of death status epilepticus and multi-organ failure. Acute liver necrosis
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	childhood
Age of Onset: 8, Age of Patient: n/a, Age of Death: 9

Reference:	Tzoulis et al, 2006; [PubMed] 51
Description:	Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, neuropathy
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 17, Age of Patient: 27, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 52
Description:	Presented with migraine like headaches, ataxia, nystagmus, neuropathy, PEO/ Ptosis onset age >30
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	childhood
Age of Onset: 12, Age of Patient: 38, Age of Death: n/a

Reference:	Tzoulis et al, 2006; [PubMed] 53
Description:	Presented with progressive gait unsteadiness and headaches, ataxia, epilepsy, status epilepticus, nystagmus, neuropathy. Died 2 months after treatment with sodium valproate, cause of death status epilepticus
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 15, Age of Patient: n/a, Age of Death: 57

Reference:	Tzoulis et al, 2006; [PubMed] 54
Description:	Presented with progressive gait unsteadiness, ataxia, epilepsy, status epilepticus, headaches, myoclonus, neuropathy, ptosis/ PEO onset age 30. Mild liver dysfunction. Cause of death status epilepticus.
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	childhood
Age of Onset: 4, Age of Patient: n/a, Age of Death: 30

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Reference:	Tzoulis et al, 2006; [PubMed] 55
Description:	Presented with speech delay, ataxia, epilepsy, status epilepticus, and headaches. Liver dysfunction and rising liver enzymes and bilirubin terminally, cause of death status epilepticus, multi-organ failure. Hepatic histology showed marked steatosis.
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	childhood
Age of Onset: 8, Age of Patient: n/a, Age of Death: 9

Reference:	Johansen et al, 2008; [PubMed] 56
Description:	Presented with focal epileptic seizures, external ophthalmoplegia and gait unsteadiness. At age 28, during her first pregnancy, she was admitted with focal epileptic seizures that were highly resistant to treatment. Two months later her symptoms worsened and included myoclonic jerks in the extremities and facial dyskinesias. Treatment with sodium valproate resulted in acute severe hepatic failure and she underwent a successful liver transplantation. At 35 mild cognitive deficit, cerebellar dysarthria, palatal tremor, facial dyskinesias, myoclonus, cerebellar and sensory ataxia and signs of peripheral neuropathy with loss of reflexes and sensory disturbance were also present
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 19, Age of Patient: 35, Age of Death: n/a

Reference:	Remes et al, 2008; [PubMed] 57
Description:	patient noticed gait and balance difficulties at age 46 years, ataxia, CPEO, cortical and cerebellar atrophy, axonal sensory polyneuropathy, Symmetrical bradykinesia and rigidity, mild tremor, paranoid delusions, During the last 2 years of life he had marked rigidity, dysphagia, myoclonic jerks and dystonia
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 46, Age of Patient: 65, Age of Death: n/a

Reference:	Uusimaa et al, 2008; [PubMed] 58
Description:	Headache, visual symptoms, migraine-like headache, Athetosis, nystagmus, emiparesis, valproic acid induced Liver failure, sepsis, pancreatitis, status epilepticus
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 14, Age of Patient: 15, Age of Death: n/a

Reference:	Uusimaa et al, 2008; [PubMed] 59
Description:	Migraine like headaches, visual symptoms, focal generalized seizures, severe liver failure, valproate induced liver failure
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 15, Age of Patient: n/a, Age of Death: 20

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Reference:	Uusimaa et al, 2008; [PubMed] 60
Description:	Seizures, status epilepticus, visual symptoms, nystagmus, valproic acid induced liver failure
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	juvenile
Age of Onset: 17, Age of Patient: 21, Age of Death: n/a

Reference:	Rouzier et al, 2013; [PubMed] 61
Description:	Parkinsonism, multiple mtDNA deletions. SANDO, Sensory ataxic neuropathy dysarthria and ophtalmoparesis.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: 37, Age of Patient: n/a, Age of Death: n/a

Reference:	Palin et al, 2012; [PubMed] 62
Description:	Gait disturbance since childhood. Early onset suggested anticipation. In his 20's he developed photophobia and general clumsiness and benign paroxysmal positional vertigo. From the age of 37 he has had unspecific sensory polyneuropathy, confirmed by electromyography. He had several simple partial seizures at the age of 39, and has mild anxiety and depression.
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	childhood
Age of Onset: 5, Age of Patient: 41, Age of Death: n/a

Reference:	Palin et al, 2012; [PubMed] 63
Description:	developed gait disturbance by the age of 35, progressing to increasing clumsiness in lower extremities, dysarthria, diplopia, and occasional amnesia at the age of 44. She developed ataxia, slight polyneuropathy, and external ophthalmoplegia. At the age of 46 she had slightly increased plasma creatine kinase levels and symmetrical cerebellar peduncular white matter signal intensity increase in brain MRI. The first epileptic seizure, requiring treatment by general anesthesia, oc- curred at the age of 55, after which she was hospitalized permanently. From her 30's, she received psychiatric care due to anxiety and depression. A neuropsychological examination revealed decrease in visual reasoning and memory functions. She deceased at the age of 56 due to pneumonia and pulmonary embolism.
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 35, Age of Patient: n/a, Age of Death: 56

Reference:	Tzoulis et al, 2013; [PubMed] 64
Description:	Ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	W748S, W748S
Age group:	childhood
Age of Onset: 12, Age of Patient: 45, Age of Death: n/a

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Reference:	Tzoulis et al, 2013; [PubMed] 65
Description:	Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	W748S, W748S
Age group:	childhood
Age of Onset: 6, Age of Patient: n/a, Age of Death: 41

Reference:	Tzoulis et al, 2013; [PubMed] 66
Description:	Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	W748S, W748S
Age group:	childhood
Age of Onset: 12, Age of Patient: n/a, Age of Death: 28

Reference:	Tzoulis et al, 2013; [PubMed] 67
Description:	Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 16, Age of Patient: n/a, Age of Death: 24

Reference:	Tzoulis et al, 2013; [PubMed] 68
Description:	Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 17, Age of Patient: n/a, Age of Death: 43

Reference:	Tzoulis et al, 2013; [PubMed] 69
Description:	Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy.
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 17, Age of Patient: 34, Age of Death: n/a

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Reference:	Sitarz et al, 2014; [PubMed] 70
Description:	Ataxia, neuropathy, PEO, MIRAS.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: n/a, Age of Patient: 36, Age of Death: n/a

Reference:	Tzoulis et al, 2014; [PubMed] 71
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 15, Age of Patient: n/a, Age of Death: 24

Reference:	Tzoulis et al, 2014; [PubMed] 72
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO
Mutations:	W748S, W748S
Age group:	childhood
Age of Onset: 6, Age of Patient: n/a, Age of Death: 41

Reference:	Tzoulis et al, 2014; [PubMed] 73
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO.
Mutations:	W748S, W748S
Age group:	childhood
Age of Onset: 12, Age of Patient: n/a, Age of Death: 28

Reference:	Tzoulis et al, 2014; [PubMed] 74
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO.
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 15, Age of Patient: n/a, Age of Death: 57

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Reference:	Tzoulis et al, 2014; [PubMed] 75
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO.
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 16, Age of Patient: n/a, Age of Death: 24

Reference:	Tzoulis et al, 2014; [PubMed] 76
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO.
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 17, Age of Patient: n/a, Age of Death: 43

Reference:	Tzoulis et al, 2014; [PubMed] 77
Description:	Epilepsy, stroke-like episode, Ataxia, Neuropathy.
Mutations:	W748S, W748S
Age group:	infantile
Age of Onset: 2, Age of Patient: n/a, Age of Death: 13

Reference:	Schicks et al, 2010; [PubMed] 78
Description:	PEO, epilepsy, early-onset cerebellar ataxia. Dysarthria, sensory neuropathy, Cerebellar atrophy.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: 22, Age of Patient: n/a, Age of Death: n/a

Reference:	Schicks et al, 2010; [PubMed] 79
Description:	early-onset ataxia, epilepsy, sensory neuropathy.
Mutations:	W748S, W748S
Age group:	childhood
Age of Onset: 12.5, Age of Patient: n/a, Age of Death: n/a

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Reference:	Synofzik et al, 2010; [PubMed] 80
Description:	Dystonia of both arms, with predominant dystonic ulnar deviation of the right upper limb with jerky wrist and finger movements. Also her feet show unpatterend jerky movements, which may be classified as myoclonus but are also similar to limb movements in benign hereditary chorea. external ophthalmoplegia, slowing of voluntary saccades and gait ataxia started.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: 33, Age of Patient: n/a, Age of Death: n/a

Reference:	Synofzik et al, 2010; [PubMed] 81
Description:	dystonic ulnar deviation of the left upper limb with distal predominance. She showed intermittent facial and jaw opening dystonia. At rest, she had marked postural instability caused by trunk ataxia, which is aggravated by motor actions like e.g. lifting the upper limbs. severe dysarthria, incomplete horizontal and vertical external ophthalmoplegia and ataxia were observed as clinical features of MIRAS. Patient 2 was only able to stand assisted for a few seconds.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: 40, Age of Patient: n/a, Age of Death: n/a

Reference:	Van Goethem et al, 2004; [PubMed] 82
Description:	plurimetabolic syndrome. At age 30 years, he noted disturbed balance, and ataxia and severe axonal neuropathy were diagnosed. On examination at age 32 years, he had slowed ocular pursuit movements but with full range of motion. He had severe gait ataxia, imbalance, and trunk ataxia, as well as clumsiness of the hands. Achilles tendon reflexes were absent. dysarthria, obesity, chronic motor axonopathy, moderate sensory neuropathy at the upper limbs, mild neurogenic atrophy.
Mutations:	W748S, W748S
SNPs:	E1143G, E1143G
Age group:	adult
Age of Onset: 30, Age of Patient: 33, Age of Death: n/a

Reference:	Arkadir et al, 2015; [PubMed] 83
Description:	A 30-year-old man with sensorineural hearing loss presented with subacute somnolence, slurred speech, and unsteady gait following treatment with peginterferon a-2b and ribavirin for chronic hepatitis C virus. Examination revealed scanning speech, horizontal nystagmus, gait ataxia, and symmetric hyporeflexia with distal sensory loss. Bilateral hypertrophic olivary degeneration.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: n/a, Age of Patient: 30, Age of Death: n/a

Reference:	Henao et al, 2016; [PubMed] 84
Description:	a unique combination of lesions in the thalamus, cerebellum and inferior olivary nucleus. ataxia, dysarthria, external ophthalmoparesis, generalized areflexia, abnormal leg pallesthesia, wide-based gait, positive, Romberg test, dysmetria, and a predominantly left dysdiadochokinesia. distal sensorimotor neuropathy.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: 24, Age of Patient: 29, Age of Death: n/a

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Reference:	Paucar et al, 2016; [PubMed] 85
Description:	progressive balance difficulties, impaired gait and coordination (ataxia), slurred speech, diplopia, and hypoacusis, insidious cognitive decline, esophoria. Upon exam, signs of both cerebellar and sensory ataxia (positive Romberg’s sign) as well as chorea, myoclonus, areflexia, and complete loss of vibration sense were found. Bradykinesia and marked postural instability. Eye examination revealed broken up smooth pursuit, nystagmus, mild dysconjugation of lateral eye movements, hypometric saccades and partial restriction of vertical gaze. Psychometric evaluation revealed deficits in information processing speed, working memory, attention, and visuospatial skills. A mild sensorineuronal hearing loss.
Mutations:	W748S, W748S
Age group:	adult
Age of Onset: 48, Age of Patient: 60, Age of Death: n/a

Reference:	Janssen et al, 2016; [PubMed] 86
Description:	Focal seizures with left visual field symptoms and motor signs. Neurological examination disclosed PEO, dysarthria, decreased reflexes, loss of proprioception distally in the legs, discrete pyramidal signs and appendicular ataxia on the left side with an ataxic gait. Mild cognitive decline was present. infratentorial white matter lesions, axonal polyneuropathy. negative myoclonus.
Mutations:	W748S, W748S
SNPs:	E1143G
Age group:	adult
Age of Onset: 26, Age of Patient: 28, Age of Death: 33.5

Reference:	Janssen et al, 2016; [PubMed] 87
Description:	He presented with two focal seizures with jerking of the right arm and leg. Brain imaging showed a T2-hyperintense lesion in the left frontal lobe. Focal status epilepticus characterized by visual hallucinations in the left visual fields. An appendicular ataxia, nystagmus and areflexia. His level of consciousness deteriorated, evolving into a refractory subtle SE. The patient died eventually after 5 months of continuous epileptic activity due to a septic shock.
Mutations:	W748S, W748S
Age group:	juvenile
Age of Onset: 17, Age of Patient: 20, Age of Death: 20

Reference:	Blok et al, 2009; [PubMed] 88
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] 89
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

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Reference:	Horvath et al, 2006; [PubMed] 90
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:	Schulte et al, 2009; [PubMed] 91
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

Reference:	Stewart et al, 2009; [PubMed] 92
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] 93
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:	Hansen et al, 2012; [PubMed] 94
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

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Reference:	Kinghorn et al, 2012; [PubMed] 95
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

Reference:	Kinghorn et al, 2012; [PubMed] 96
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] 97
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] 98
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] 99
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

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Reference:	Lax et al, 2012a; [PubMed] 100
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

Reference:	Lax et al, 2012a; [PubMed] 101
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:	Paus et al, 2008; [PubMed] 102
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

Reference:	Rouzier et al, 2013; [PubMed] 103
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:	Roshal et al, 2011; [PubMed] 104
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

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Reference:	Tuladhar et al, 2013; [PubMed] 105
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] 106
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

Reference:	Tzoulis et al, 2013; [PubMed] 107
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] 108
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] 109
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

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Reference:	Lax et al, 2012b; [PubMed] 110
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] 111
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

Reference:	Tzoulis et al, 2014; [PubMed] 112
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] 113
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:	Janssen et al, 2016; [PubMed] 114
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

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Reference:	Ashley et al, 2008; [PubMed] 115
Description:	Reported as Alpers, onset at 6 years, presenting encephalopathy with epilepsy, hepatopathy absent, and movement disorder (ataxia).
Mutations:	G848S, W748S
Age group:	childhood
Age of Onset: 6, Age of Patient: n/a, Age of Death: n/a

Reference:	Isohanni et al, 2011; [PubMed] 116
Description:	Partial status epilepticus, epilepsia partialis, continua, hemiparesis, myoclonus, loss of vision, optical atrophy, pschomotor regression, liver dysfunction, death via pneumonia.
Mutations:	G848S, W748S
SNPs:	E1143G
Age group:	infantile
Age of Onset: 1, Age of Patient: n/a, Age of Death: 11

Reference:	Taanman et al, 2009; [PubMed] 117
Description:	Onset at 6.5 years with alpers syndrome and death at 7.8 years. 23% mtDNA copy number in liver.
Mutations:	G848S, W748S
SNPs:	E1143G
Age group:	childhood
Age of Onset: 6.5, Age of Patient: n/a, Age of Death: 7.8

Reference:	Tang et al, 2011; [PubMed] 118
Description:	Headaches/migrains, seizures, intractable seizure, cortical blindness. 32% mtDNA copy number in blood.
Mutations:	G848S, W748S
Age group:	childhood
Age of Onset: n/a, Age of Patient: 7, Age of Death: n/a