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34 patient data entries in database for cluster 2. Entry
# | | Mutations | | allele 1 | allele 2 |
| Clinical representation | Symptoms | Age group | Age of onset | Age of patient | Age of death | Reference | | | 281 | | G517V2
| Global developmental delay, Central hypotonia, Nystagmus and eye surgery, Autistic features, Generalized seizure, Hypnic myoclonia, Intermittent hypoglycemia, Abnormal MRI | | | 0.7 | 4.5 | n/a | Burusnukul and de los Reyes, 2009; [view data] | | 283 | | T251I
P587L2
| Global developmental delay, Central hypotonia, Torticollis, feeding difficulty at birth, myoclonic seizure, horizontal nystagmus, Intermittent estropia, Abnormal MRI | | | 0.4 | n/a | n/a | Burusnukul and de los Reyes, 2009; [view data] | | 293 | | G517V2
| diagnosed with type I DM at age 2, diagnosed with adrenal insufficiency and hypothyroidism at age 10, first seizure or dystonic crisis at age 16 years, then neurologic, intensive care unit, and psychiatric admissions for dystonic crises, status epilepticus, nonconvulsive status epilepticus, encephalopathy, depression, suicidal ideation, and psychosis. Elevated lactate, chronic myopathic changes, developmental delay | | | 2 | n/a | n/a | Hopkins et al, 2010; [view data] | | 424 | R722H
| G517V2
| Onset at 4 months with generalized tonic-clonic seizure, evolved to status epilepticus, treated with valproate, Progressive encephalopathy, and psychomotor development deficient by age 2, mentally retarded, ataxic and hyperkinetic. At the last follow-up visit at age 17 years, he was severely retarded, autistic, and ataxic. During 12 months of valproate treatment serum alanine aminotransferase (ALAT) increased from 29 to 71 U/L (normal < 40 U/L), and after discontinuation of the medication, ALAT values varied between 5 and 12 U/L. | | | 0.33 | 17 | n/a | Bolszak et al, 2009; [view data] | | 458 | | G517V2
| Diffuse hypotonia, hypoactive reflexes, and roving eye movements. Decreased vis- ual acuity, mild bilateral macular pigmentary changes, normal refractive indices, bilateral ptosis, diffuse cerebral atrophy, and disconjugate, nystagmoid eye movements. In addition to G517V, affected by gene CLN5 c.61C>T, p.Pro21Ser and de novo exon 3 deletion. | | | 0.1 | n/a | n/a | Staropoli et al, 2012; [view data] | | 530 | P116Q
| P587L2
T251I
| 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. | | | 7 | 14 | n/a | Scuderi et al, 2015; [view data] | | 531 | P116Q
| T251I
P587L2
| 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. | | | 3 | 8 | n/a | Scuderi et al, 2015; [view data] | | 282 | | G517V2
| Migraines, Complex partial seizure with secondarily generalization, mild developmental delay, muscle cramps and experienced easy fatigability, | | | 7 | n/a | n/a | Burusnukul and de los Reyes, 2009; [view data] | | 294 | | G517V2
| diagnosed with type I DM at age 5, diagnosed with adrenal insufficiency and hypothyroidism at age 11, presented to neurology at age 17 years, for 2 weeks of headache and recent onset of left facial twitching. neurologic, intensive care unit, and psychiatric admissions for dystonic crises, status epilepticus, nonconvulsive status epilepticus, encephalopathy, depression, suicidal ideation, and psychosis. Elevated lactate, developmental delay | | | 5 | n/a | n/a | Hopkins et al, 2010; [view data] | | 532 | | T251I
P587L2
| 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. | | | n/a | 10 | n/a | Scuderi et al, 2015; [view data] | | 508 | | T251I
P587L2
| 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). | | - | movement disorder (ataxia) | |
| | n/a | 4 | 4.75 | Harris et al, 2010; [view data] | | 354 | | G517V2
| neuropathy, dysphagia/ dysarthria, slowly progressive ataxia, hearing loss, slow gastrointestinal transit times, proximal myopathy. Patient #5. | | - | movement disorder (ataxia) | |
| | n/a | 56 | n/a | Woodbridge et al, 2012; [view data] | | 514 | | S511N2
| progressive bilateral ptosis in her early 20s followed by external ophthalmoplegia. She came to medical attention through an infertility clinic investigating her primary ovarian failure. | | - | external ophthalmoplegia | |
| | 20 | 30 | n/a | Hudson et al, 2007; [view data] | | 682 | D122Y
Q1236H
Y837C
| K601E2
| Unsteady walk, and showed tremor in both legs when standing. Difficulty in concentrating. Dysarthria. No deep tendon reflexes were evident. Sensory axonal neuropathy. Hyperintensities in images of the subcortical frontal and temporal white substances. myoclonia and tonic-clonic seizures. sensory axonal neuropathy in the lower limbs, moderate dysarthria, and an ataxic gait. | | - | movement disorder (ataxia) | |
| - | demyelinating neuropathy | |
| | 56 | 61 | n/a | Zabalza et al, 2014; [view data] | | 533 | | T251I
P587L2
| 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. | | | 29 | 37 | n/a | Scuderi et al, 2015; [view data] | | 572 | R3P
| A467T2
| ptosis, opthalmoplegia, dysphonia, dysphagia, muscle weakness, loss of weight, distal sensory neuropathy, areflexia. | | | 20 | 61 | n/a | Van Goethem et al, 2001; [view data] | | 573 | R3P
| A467T2
| ptosis, opthalmoplegia, dysphonia, dysphagia, distal sensory neuropathy, areflexia. | | | 30 | 58 | n/a | Van Goethem et al, 2001; [view data] | | 576 | | G517V2
| PEO, late-onset ataxia, dysarthria, ptosis, pyramidal tract signs, psychiatric disorders | | - | movement disorder (ataxia) | |
| | 44 | n/a | n/a | Schicks et al, 2010; [view data] | | 577 | | G517V2
| early-onset ataxia, dysarthria, pyramidal tract signs, psychiatric disorders, Cerebellar atrophy, Extrapyramidal signs. | | - | movement disorder (ataxia) | |
| | 22 | n/a | n/a | Schicks et al, 2010; [view data] | | 644 | | R617C2
| Lactic acidosis, Muscle weakness, exercise intolerance, hearing loss, arhytthmia | | | 39 | n/a | n/a | Wong et al, 2008; [view data] | | 681 | D122Y
Q1236H
Y837C
| K601E2
| ataxia, dysarthria and sensory axonal polyneuropathy. At age 52, the patient developed instability upon walking and paraesthesia in lower limbs, when no other symptoms were apparent. Clinical examination at age 67 revealed dysarthria, gait ataxia, hyporeflexia and tactile hypoestesia. Atrophy of the cerebellar hemispheres. Cognitive decline. left hemiparesis related to a non-traumatic subdural haematoma that required neurosurgical treatment, and began to experience myoclonus and tonic-clonic seizures. weak bilateral palpebral ptosis. | | - | movement disorder (ataxia) | |
| - | axonal sensorimotor polyneuropathy | |
| | 52 | 67 | n/a | Zabalza et al, 2014; [view data] | | 242 | | A467T2
| This 64-year-old woman, the mother of the index patient, developed slowly progressive blepharoptosis at the age of 45. She underwent blepharoplasty at the age of 58. In the neurological examination at the age of 63, she had ptosis, but no other neurological deficits. Late onset ptosis. | | | 45 | 64 | n/a | Luoma et al, 2005; [view data] | | 513 | | S511N2
| bilateral ptosis. | | | n/a | 58 | n/a | Hudson et al, 2007; [view data] | | 512 | | S511N2
| bilateral ptosis. | | | n/a | 65 | n/a | Hudson et al, 2007; [view data] | | 511 | | S511N2
| bilateral ptosis. | | | n/a | 60 | n/a | Hudson et al, 2007; [view data] | | 509 | | S511N2
| PEO, Ptosis, limb ataxia and progressive hearing loss. On examination, she had prominent ptosis, mild bilateral facial weakness, symmetric hip flexion weakness, and absent lower limb tendon reflexes with a mild gait ataxia. axonal sensory neuropathy with additional myopathic features. Muscle biopsy revealed an increased range of muscle fiber diameters, 20% being cytochrome c oxidase–deficient. | | - | movement disorder (ataxia) | |
| | 40 | 61 | n/a | Hudson et al, 2007; [view data] | | 475 | | T251I
P587L2
| 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). | | | 53 | 58 | n/a | Aitken et al, 2009; [view data] | | 443 | | K512M2
| Developed first neurologic problems in his thirties. Parkinsonism, bilateral ptosis, double vision, facial weakness, progressive ophthalmoplegia, shuffling gait and overall slowness of movements. He experienced a gradual progression of his rigidity, bradykinesia without any significant asymmetry, hypophonia and within 10–15 years he also developed camptocormia with subsequent postural instability. Dementia diagnosed at the age of 75 years. Family history was positive for external ophthalmople- gia and Parkinson’s disease diagnosed in his father and brother. | | | 30 | 79 | n/a | Dolhun et al, 2013; [view data] | | 442 | | P765T2
| drooping eyelids (without daytime fluctuation), slurred speech, dramatic weight loss, progressive gait instability, leg numbness and inability to feel the ground under her feet, anorexia, gastroparesis, peripheral neuropathy, sensory ataxia, SANDO. The patient's deceased mother had a similar bilateral ptosis, without any other ocular signs, her parents were not consanguineous. The patient has one healthy daughter. bilateral ptosis, complete ophthalmoplegia, optic discs atrophy. Flaccid type dysarthria, mild upper and lower limb muscle weakness with distal predominance. Deep tendon jerks were absent, plantar responses were flexor. Muscular tone was normal. | | - | movement disorder (ataxia) | |
| | 42 | 52 | n/a | Bostan et al, 2012; [view data] | | 429 | | A467T2
| LS-like, sensorimotor neuropathy. At 56 years old, patient 13 developed a motor neuron disease with severe tetraparesis, dysphonia and respiratory insufficiency leading to death a few years later. Muscular biopsy was strongly evocative of mitochondrial disease with a generalized RC deficiency, multiple mtDNA deletions and decreased mtDNA copy number in the muscle (39%). | | | 56 | 56 | 60 | Rouzier et al, 2013; [view data] | | 409 | | A467T2
| at age 24 developed PEO and weakness of neck and proximal limb muscles. presence of multiple mtDNA deleted species, unsteady, broad-based gait. At age 32 she had complete PEO, bradykinesia, cogwheel rigidity, slurred speech, dysphagia, dysmetria, positive Romberg sign, reduced arm swing, and intermittent bilateral postural-action tremor. axonal sensorimotor neuropathy, severe depression, insomnia, and nocturnal panic attacks Has also mutation ANT1 gene (V289M) | | - | axonal sensorimotor polyneuropathy | |
| | 24 | 42 | n/a | Galassi et al, 2008; [view data] | | 245 | | A467T2
| probable mild blepharoptosis, early onset ptosis | | | n/a | 23 | n/a | Luoma et al, 2005; [view data] | | 244 | | A467T2
| This 50-year-old woman developed progressive blepharoptosis slowly at the age of 40. She underwent blepharoplasty at the age of 47. Her neurological examination at the age of 50 was normal. Late onset ptosis | | | 40 | 50 | n/a | Luoma et al, 2005; [view data] | | 243 | | A467T2
| This 66-year-old woman developed progressive blepharoptosis slowly at the age of 50. She underwent blepharoplasty at the age of 62, and in the same year, she suffered a transitory ischemic attack. At the age of 66, no clinical findings except ptosis were detectable. Late onset ptosis. | | | 50 | 66 | n/a | Luoma et al, 2005; [view data] |
1-5 pathogenic cluster assignment of mutations. Mutations displayed without a superscript number are outside of the assigned pathogenic clusters. See cluster definitions for details. Number of displayed patient cases: 34
Number of patient cases marked as outliers: 3 (cases excluded from avg: 283, 508, 409)
Avg age of onset in displayed cases: 31.1
Std dev in onset in displayed cases: 21.0
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