POLG Pathogenicity Prediction Server

SNPs:

E1143G

Age group:

adult

Age of Onset: n/a, Age of Patient: 47, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

childhood

Age of Onset: 5, Age of Patient: 13, Age of Death: 14

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

childhood

Age of Onset: 11, Age of Patient: 24, Age of Death: n/a

Reference:

Sarzi et al, 2007;

[PubMed]

Description:

Onset with walking difficulties, seizures at 2.5 years, hepatocellular insufficiency after valproate treatment, alpers syndrome, Liver mtDNA depletion.

Mutations:

SNPs:

E1143G

Age group:

infantile

Age of Onset: 2, Age of Patient: n/a, Age of Death: 3

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

juvenile

Age of Onset: 19, Age of Patient: n/a, Age of Death: 19

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

juvenile

Age of Onset: 14, Age of Patient: n/a, Age of Death: 23

Reference:

[PubMed]

Description:

Presented with epilepsy, ataxia, nystagmus, neuropathy, ptosis/ PEO onset at age 65

Mutations:

SNPs:

E1143G

Age group:

adult

Age of Onset: 55, Age of Patient: 74, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

childhood

Age of Onset: 10, Age of Patient: n/a, Age of Death: 10

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

adult

Age of Onset: 20, Age of Patient: n/a, Age of Death: 20

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

juvenile

Age of Onset: 15, Age of Patient: n/a, Age of Death: 21

Reference:

[PubMed]

Description:

Presented with progressive gait unsteadiness, ataxia, headaches, myoclonus, neuropathy, PEO, ptosis onset at age 44

Mutations:

SNPs:

E1143G

Age group:

adult

Age of Onset: 36, Age of Patient: 50, Age of Death: n/a

Reference:

[PubMed]

Description:

Presented with progressive gait unsteadiness, ataxia, headaches, neuropathy, PEO ptosis onset age 25

Mutations:

SNPs:

E1143G

Age group:

adult

Age of Onset: 24, Age of Patient: 43, Age of Death: n/a

Reference:

Paus et al, 2008;

[PubMed]

Description:

Presented with PEO, mild bilateral ptosis, dysarthria, ataxia, and neuropathy

Mutations:

SNPs:

E1143G

Age group:

adult

Age of Onset: 36, Age of Patient: 37, Age of Death: n/a

Reference:

Amiot et al, 2009;

[PubMed]

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

Reference:

Palin et al, 2012;

[PubMed]

Description:

No neurological symptoms, but type-2 diabetes and hypertension.

Mutations:

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]

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:

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]

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:

SNPs:

E1143G

Age group:

childhood

Age of Onset: 12, Age of Patient: 52, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

juvenile

Age of Onset: 17, Age of Patient: 20, Age of Death: 23

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

juvenile

Age of Onset: 18, Age of Patient: 18.7, Age of Death: n/a

Reference:

[PubMed]

Description:

reported as Alpers, onset at 16 years, presenting encephalopathy with epilepsy, hepatopathy, and movement disorder (ataxia). 108% mtDNA copy number in muscle.

Mutations:

Age group:

juvenile

Age of Onset: 16, Age of Patient: n/a, Age of Death: n/a

Reference:

Schulte et al, 2009;

[PubMed]

Description:

cerebellar ataxia, dysarthria/dysphagia, sensory neuropathy, PEO, epilepsy, moderate cerebellar atrophy.

Mutations:

Age group:

adult

Age of Onset: 22, Age of Patient: n/a, Age of Death: n/a

Reference:

[PubMed]

Description:

Ataxia, peripheral neuropathy, exercise intolerance, easy fatigueability, cerebellar atrophy, abnormal MRI. 82% mtDNA copy number in blood.

Mutations:

Age group:

adult

Age of Onset: n/a, Age of Patient: 30, Age of Death: n/a

Reference:

[PubMed]

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:

Q497H, Q497H, 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]

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:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 23, Age of Patient: 38, Age of Death: n/a

Reference:

Winterthun et al, 2005;

[PubMed]

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:

[PubMed]

Description:

Onset 33 years with neuropathy, myopathy, SANDO, lactic acidosis, PEO.

Mutations:

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]

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:

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]

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:

Pelayo-Negro et al, 2012;

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 32, Age of Patient: 33, Age of Death: n/a

Reference:

[PubMed]

Description:

ataxia, sensory neuropathy, dysarthria, and external ophthalmoparesis

Mutations:

Age group:

adult

Age of Onset: 30, Age of Patient: 51, Age of Death: n/a

Reference:

Tang et al, 2012;

[PubMed]

Description:

migraine, ptosis, PEO, exercise intolerance, sensorimotor peripheral neuropathy, ataxia, pseudoobstruction, constipation, and sensorineural hearing loss,

Mutations:

SNPs:

S28C

Age group:

adult

Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a

Reference:

[PubMed]

Description:

Onset with balance disturbances and neuropathy, Gait and limb ataxia, Dysarthria, restricted eye movements, ptosis, Cognitive impairment, Obesity, cramps, sensory motor polyneuropathy

Mutations:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 38, Age of Patient: 44, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 38, Age of Patient: 51, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 27, Age of Patient: 38, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 32, Age of Patient: 46, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 27, Age of Patient: 42, Age of Death: n/a

Reference:

[PubMed]

Description:

Onset with epilepsy, Gait and limb ataxia, Epilepsy, Dysarthria, Nystagmus, diplopia, Psychiatric symptoms, Obesity, sensory motor polyneuropathy

Mutations:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 24, Age of Patient: 55, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 16, Age of Patient: 37, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 23, Age of Patient: 45, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 17, Age of Patient: 45, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 19, Age of Patient: 44, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 28, Age of Patient: 51, Age of Death: n/a

Reference:

[PubMed]

Description:

Onset with neuropathy, Gait and limb ataxia, Dysarthria, Dysphagia, other eye-movement abnormalities, Cognitive impairment, Psychiatric symptoms, Obesity, sensory motor polyneuropathy

Mutations:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 41, Age of Patient: 58, Age of Death: n/a

Reference:

[PubMed]

Description:

Onset with neuropathy, Gait and limb ataxia, tremor, Dysarthria, Nystagmus, Psychiatric symptoms, Muscle strength decreased, amyotrophy, pes cavus, sensory motor polyneuropathy

Mutations:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 36, Age of Patient: 51, Age of Death: n/a

Reference:

[PubMed]

Description:

Onset with tremor, Gait and limb ataxia, Epilepsy, Myoclonus, Involuntary movements, Dysarthria, eye muscle weakness, Cognitive impairment, Psychiatric symptoms, Muscle strength decreased.

Mutations:

SNPs:

E1143G, E1143G

Age group:

childhood

Age of Onset: 5, Age of Patient: n/a, Age of Death: 35

Reference:

[PubMed]

Description:

Presented with epilepsy, ataxia, status epilepticus, headaches, myoclonus, neuropathy

Mutations:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 18, Age of Patient: 19, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 19, Age of Patient: 33, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

childhood

Age of Onset: 10, Age of Patient: n/a, Age of Death: 22

Reference:

[PubMed]

Description:

Presented with epilepsy, status epilepticus, nystagmus, neuropathy

Mutations:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 17, Age of Patient: 18, Age of Death: n/a

Reference:

[PubMed]

Description:

Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, myoclonus, neuropathy, ptosis/ PEO onset at age 26

Mutations:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 17, Age of Patient: 38, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

childhood

Age of Onset: 8, Age of Patient: n/a, Age of Death: 9

Reference:

[PubMed]

Description:

Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, neuropathy

Mutations:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 17, Age of Patient: 27, Age of Death: n/a

Reference:

[PubMed]

Description:

Presented with migraine like headaches, ataxia, nystagmus, neuropathy, PEO/ Ptosis onset age >30

Mutations:

SNPs:

E1143G, E1143G

Age group:

childhood

Age of Onset: 12, Age of Patient: 38, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 15, Age of Patient: n/a, Age of Death: 57

Reference:

[PubMed]

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:

SNPs:

E1143G, E1143G

Age group:

childhood

Age of Onset: 4, Age of Patient: n/a, Age of Death: 30

Reference:

[PubMed]

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:

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]

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:

Age group:

juvenile

Age of Onset: 19, Age of Patient: 35, Age of Death: n/a

Reference:

Remes et al, 2008;

[PubMed]

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:

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]

Description:

Headache, visual symptoms, migraine-like headache, Athetosis, nystagmus, emiparesis, valproic acid induced Liver failure, sepsis, pancreatitis, status epilepticus

Mutations:

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]

Description:

Migraine like headaches, visual symptoms, focal generalized seizures, severe liver failure, valproate induced liver failure

Mutations:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 15, Age of Patient: n/a, Age of Death: 20

Reference:

Uusimaa et al, 2008;

[PubMed]

Description:

Seizures, status epilepticus, visual symptoms, nystagmus, valproic acid induced liver failure

Mutations:

SNPs:

E1143G, E1143G

Age group:

juvenile

Age of Onset: 17, Age of Patient: 21, Age of Death: n/a

Reference:

[PubMed]

Description:

Parkinsonism, multiple mtDNA deletions. SANDO, Sensory ataxic neuropathy dysarthria and ophtalmoparesis.

Mutations:

Age group:

adult

Age of Onset: 37, Age of Patient: n/a, Age of Death: n/a

Reference:

Palin et al, 2012;

[PubMed]

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:

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]

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:

SNPs:

E1143G, E1143G

Age group:

adult

Age of Onset: 35, Age of Patient: n/a, Age of Death: 56

Reference:

[PubMed]

Description:

Ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).

Mutations:

Age group:

childhood

Age of Onset: 12, Age of Patient: 45, Age of Death: n/a

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).

Mutations:

Age group:

childhood

Age of Onset: 6, Age of Patient: n/a, Age of Death: 41

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).

Mutations:

Age group:

childhood

Age of Onset: 12, Age of Patient: n/a, Age of Death: 28

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).

Mutations:

Age group:

juvenile

Age of Onset: 16, Age of Patient: n/a, Age of Death: 24

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).

Mutations:

Age group:

juvenile

Age of Onset: 17, Age of Patient: n/a, Age of Death: 43

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episodes, ataxia, peripheral neuropathy.

Mutations:

Age group:

juvenile

Age of Onset: 17, Age of Patient: 34, Age of Death: n/a

Reference:

Sitarz et al, 2014;

[PubMed]

Description:

Ataxia, neuropathy, PEO, MIRAS.

Mutations:

Age group:

adult

Age of Onset: n/a, Age of Patient: 36, Age of Death: n/a

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy

Mutations:

Age group:

juvenile

Age of Onset: 15, Age of Patient: n/a, Age of Death: 24

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO

Mutations:

Age group:

childhood

Age of Onset: 6, Age of Patient: n/a, Age of Death: 41

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO.

Mutations:

Age group:

childhood

Age of Onset: 12, Age of Patient: n/a, Age of Death: 28

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO.

Mutations:

Age group:

juvenile

Age of Onset: 15, Age of Patient: n/a, Age of Death: 57

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO.

Mutations:

Age group:

juvenile

Age of Onset: 16, Age of Patient: n/a, Age of Death: 24

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy, PEO.

Mutations:

Age group:

juvenile

Age of Onset: 17, Age of Patient: n/a, Age of Death: 43

Reference:

[PubMed]

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy.

Mutations:

Age group:

infantile

Age of Onset: 2, Age of Patient: n/a, Age of Death: 13

Reference:

Schicks et al, 2010;

[PubMed]

Description:

PEO, epilepsy, early-onset cerebellar ataxia. Dysarthria, sensory neuropathy, Cerebellar atrophy.

Mutations:

Age group:

adult

Age of Onset: 22, Age of Patient: n/a, Age of Death: n/a

Reference:

Schicks et al, 2010;

[PubMed]

Description:

early-onset ataxia, epilepsy, sensory neuropathy.

Mutations:

Age group:

childhood

Age of Onset: 12.5, Age of Patient: n/a, Age of Death: n/a

Reference:

Synofzik et al, 2010;

[PubMed]

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:

Age group:

adult

Age of Onset: 33, Age of Patient: n/a, Age of Death: n/a

Reference:

Synofzik et al, 2010;

[PubMed]

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:

Age group:

adult

Age of Onset: 40, Age of Patient: n/a, Age of Death: n/a

Reference:

Van Goethem et al, 2004;

[PubMed]

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:

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]

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:

Age group:

adult

Age of Onset: n/a, Age of Patient: 30, Age of Death: n/a

Reference:

Henao et al, 2016;

[PubMed]

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:

Age group:

adult

Age of Onset: 24, Age of Patient: 29, Age of Death: n/a

Reference:

Paucar et al, 2016;

[PubMed]

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:

Age group:

adult

Age of Onset: 48, Age of Patient: 60, Age of Death: n/a

Reference:

[PubMed]

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:

SNPs:

E1143G

Age group:

adult

Age of Onset: 26, Age of Patient: 28, Age of Death: 33.5

Reference:

[PubMed]

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:

Age group:

juvenile

Age of Onset: 17, Age of Patient: 20, Age of Death: 20

Reference:

Blok et al, 2009;

[PubMed]

Description:

MELAS-like, features including occipital lobe epilepsy.

Mutations:

Age group:

juvenile

Age of Onset: n/a, Age of Patient: 19, Age of Death: n/a

Reference:

Blok et al, 2009;

[PubMed]

Description:

Occipital lobe epilepsy, myoclonus, cognitive delay, polyneuropathy, cerebellar ataxia.

Mutations:

Age group:

adult

Age of Onset: n/a, Age of Patient: 40, Age of Death: n/a

Reference:

Horvath et al, 2006;

[PubMed]

Description:

Onset at 34 years with PEO, ataxia, dysphagia, myopathy, neuropathy and Diabetes.

Mutations:

Age group:

adult

Age of Onset: 34, Age of Patient: n/a, Age of Death: n/a

Reference:

Schulte et al, 2009;

[PubMed]

Description:

Dysarthria, sensory neuropathy, PEO, minor cognitive dysfunction, depression.

Mutations:

Age group:

adult

Age of Onset: 34, Age of Patient: n/a, Age of Death: n/a

Reference:

Stewart et al, 2009;

[PubMed]

Description:

PEO, ataxia, seizures, ptosis, bilateral deafness, myopathy, dysarthria, peripheral neuropathy, multiple mtDNA deletions. 5% COX deficient fibers, 2% RRF.

Mutations:

Age group:

adult

Age of Onset: 39, Age of Patient: n/a, Age of Death: n/a

Reference:

[PubMed]

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:

Age group:

juvenile

Age of Onset: n/a, Age of Patient: 18, Age of Death: n/a

Reference:

Hansen et al, 2012;

[PubMed]

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:

Age group:

adult

Age of Onset: 23, Age of Patient: 48, Age of Death: n/a

Reference:

Kinghorn et al, 2012;

[PubMed]

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:

Age group:

juvenile

Age of Onset: n/a, Age of Patient: 18, Age of Death: 65

Reference:

Kinghorn et al, 2012;

[PubMed]

Description:

Diplopia, partial ophthalmoparesis in all directions of gaze and dysarthria, sensory neuropathy, COX-deficient fibers, multiple mtDNA deletions,

Mutations:

Pelayo-Negro et al, 2012;

Age group:

adult

Age of Onset: n/a, Age of Patient: 50, Age of Death: n/a

Reference:

[PubMed]

Description:

ataxia, sensory neuropathy, dysarthria, and external ophthalmoparesis

Mutations:

Age group:

adult

Age of Onset: 30, Age of Patient: 50, Age of Death: n/a

Reference:

[PubMed]

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:

Age group:

adult

Age of Onset: 41, Age of Patient: 48, Age of Death: n/a

Reference:

[PubMed]

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:

Age group:

adult

Age of Onset: 34, Age of Patient: 47, Age of Death: n/a

Reference:

[PubMed]

100

Description:

Peripheral neuropathy, ataxia, epilepsy, COX-deficient fibers, presence of mitochondrial dna deletions in muscle, Moderate sensory neuronopathy

Mutations:

Age group:

juvenile

Age of Onset: 16, Age of Patient: 18, Age of Death: n/a

Reference:

[PubMed]

101

Description:

Peripheral neuropathy, ataxia, epilepsy, presence of mitochondrial dna deletions in muscle,

Mutations:

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:

Age group:

adult

Age of Onset: 28, Age of Patient: 39, Age of Death: n/a

Reference:

[PubMed]

103

Description:

R-EPC (refractory epilepsia partialis continua), axonal neuropathy, cerebellar ataxia, hyperintensity of rolandic, occipital and cerebellar cortex and dentate nucleus.

Mutations:

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:

Age group:

juvenile

Age of Onset: 15, Age of Patient: 16, Age of Death: n/a

Reference:

Tuladhar et al, 2013;

[PubMed]

105

Description:

abnormal gait, ataxia, PEO, and jerky torticollis, mild cerebellar atrophy, sensory neuronopathy.

Mutations:

Age group:

adult

Age of Onset: 43, Age of Patient: 45, Age of Death: n/a

Reference:

[PubMed]

106

Description:

Ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).

Mutations:

Age group:

adult

Age of Onset: 24, Age of Patient: 50, Age of Death: n/a

Reference:

[PubMed]

107

Description:

Ataxia, peripheral neuropathy, progressive external ophthalmoplegia (PEO).

Mutations:

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:

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:

Age group:

adult

Age of Onset: 49, Age of Patient: 56, Age of Death: n/a

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:

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:

Age group:

adult

Age of Onset: n/a, Age of Patient: 39, Age of Death: n/a

Reference:

[PubMed]

112

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy.

Mutations:

Age group:

juvenile

Age of Onset: 13, Age of Patient: n/a, Age of Death: 21

Reference:

[PubMed]

113

Description:

Epilepsy, stroke-like episode, Ataxia, Neuropathy.

Mutations:

Age group:

juvenile

Age of Onset: 14, Age of Patient: n/a, Age of Death: 23

Reference:

[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:

Age group:

adult

Age of Onset: 21, Age of Patient: 47, Age of Death: n/a

Reference:

[PubMed]

115

Description:

Reported as Alpers, onset at 6 years, presenting encephalopathy with epilepsy, hepatopathy absent, and movement disorder (ataxia).

Mutations:

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:

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:

SNPs:

E1143G

Age group:

childhood

Age of Onset: 6.5, Age of Patient: n/a, Age of Death: 7.8

Reference:

[PubMed]

118

Description:

Headaches/migrains, seizures, intractable seizure, cortical blindness. 32% mtDNA copy number in blood.

Mutations:

Age group:

childhood

Age of Onset: n/a, Age of Patient: 7, Age of Death: n/a

Reference:

[PubMed]

119

Description:

Hypotonia, myoclonus, or myoclonic seizures, intractable seizure, hepatic failure, abnormal EEG. 38% mtDNA copy number in blood.

Mutations:

Age group:

childhood

Age of Onset: n/a, Age of Patient: 5, Age of Death: n/a

Reference:

[PubMed]

120

Description:

hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion

Mutations:

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.7, Age of Patient: n/a, Age of Death: 2.5

Reference:

[PubMed]

121

Description:

hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion, microvesicular steatosis,

Mutations:

SNPs:

E1143G

Age group:

infantile

Age of Onset: 1, Age of Patient: n/a, Age of Death: 6.5

Reference:

[PubMed]

122

Description:

hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion, microvesicular steatosis.

Mutations:

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.1, Age of Patient: n/a, Age of Death: 0.9

Reference:

[PubMed]

123

Description:

hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, microvesicular steatosis, fibrosis

Mutations:

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 1

Reference:

Nguyen et al, 2005;

[PubMed]

124

Description:

Refractory seizures, psychomotor regression, liver disease, presenting symptom was status epilepticus, Transient hypoglycemia, Transient lactic acidemia

Mutations:

SNPs:

E1143G

Age group:

infantile

Age of Onset: 1, Age of Patient: n/a, Age of Death: 1.7

Reference:

Wolf et al, 2009;

[PubMed]

125

Description:

Developemental delay, status epilepticus onset at 6 years 7 months, valproic acid therapy 6 weeks, liver failure with transplant, epilepsia partialis continua, elevated CSF lactate, elevated CSF protein, mtDNA depletion in liver

Mutations:

Age group:

infantile

Age of Onset: 6.6, Age of Patient: 7.8, Age of Death: n/a

Reference:

Wolf et al, 2009;

[PubMed]

126

Description:

status epilepticus onset epilepsia partialis continua, elevated CSF lactate, elevated CSF protein,

Mutations:

Age group:

childhood

Age of Onset: 10.67, Age of Patient: n/a, Age of Death: 11.5

Reference:

Saneto et al, 2010;

[PubMed]

127

Description:

seizure onset at 2 years, complex partial seizure and epilepsia partialis continua myoclonus, Truncal ataxia, intention tremor

Mutations:

Age group:

infantile

Age of Onset: 2, Age of Patient: 4, Age of Death: n/a

Reference:

Hunter et al, 2011;

[PubMed]

128

Description:

Myoclonic Seizures, Generalized tonic-clonic seizures, Focal motor seizures, Epilepsia partialis continua, Developmental Delay or Regression, ataxia, Abnormal Liver Enzymes, Serum Lactate, Alpers

Mutations:

Age group:

childhood

Age of Onset: 6, Age of Patient: n/a, Age of Death: 6.75

Reference:

Hunter et al, 2011;

[PubMed]

129

Description:

Myoclonic Seizures, Generalized tonic-clonic seizures, Focal motor seizures, Epilepsia partialis continua, Developmental Delay or Regression, ataxia, Abnormal Liver Enzymes, Serum Lactate, liver mtDNA depletion, Alpers

Mutations:

Age group:

infantile

Age of Onset: 2, Age of Patient: n/a, Age of Death: 6.33

Reference:

[PubMed]

130

Description:

Hearing loss, Ataxia Neuropathy Spectrum, Seizures, dementia, developmental delay

Mutations:

A467T, Q497H, W748S

SNPs:

E1143G

Age group:

juvenile

Age of Onset: 17, Age of Patient: n/a, Age of Death: n/a

Reference:

[PubMed]

131

Description:

developmental delay, dementia, seizures, Alpers, Family history of Alpers syndrome.

Mutations:

Brunetti-Pierri et al, 2008;

SNPs:

E1143G

Age group:

infantile

Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a

Reference:

[PubMed]

132

Description:

He exhibited a very similar phenotype to his sister, with a catastrophic onset of intractable seizures at the age of 9 months, progressive encephalopathy with epilepsia partialis continua and myoclonic jerks, and developmental regression. MRI imaging was not performed.

Mutations:

Brunetti-Pierri et al, 2008;

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.5, Age of Patient: 1.25, Age of Death: n/a

Reference:

[PubMed]

133

Description:

Mutations:

Brunetti-Pierri et al, 2008;

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.5, Age of Patient: 1.25, Age of Death: n/a

Reference:

[PubMed]

134

Description:

The index patient presented at the age of 8 months with microcephaly, seizures, and developmental delay. From the time of the first observation she rapidly developed epilepsia partialis continua, multifocal myoclonic jerks, and progressive psychomotor retardation. MRI performed at 8 months was generally unremarkable. By 9 months of age the brain MRI showed signifi cant changes including a diffuse severe cerebral and cerebellar atrophy involving gray and white matter.

Mutations:

SNPs:

E1143G

Age group:

infantile

Age of Onset: n/a, Age of Patient: 0.6, Age of Death: 1

Reference:

Ferrari et al, 2005;

[PubMed]

135

Description:

An apparently myogenic torticollis was noticed after a few months of life; at 10 months, he had two episodes of sudden head drop, followed by the onset of psychomotor arrest/ regression, hypotonia, ataxia and focal myoclonus of the right upper limb. In the following weeks, the myoclonus became subcontinuous, and was associated with rapidly progressive, severe generalized hypotonia and weakness requiring ventilatory assistance. Seizures were partially controlled with a combination of topiramate, clobazam and phenylbarbiturate. symmetrical lesions of the basal ganglia, thalami, cerebellar dentate nuclei and left occipital cortical and subcortical regions. abnormal accumulation of lactic acid in the putamen and a reduction of the N-acetyl aspartate. cholestatic jaundice, hypoglycaemia and hypocoagulation. The diagnostic conclusion was Alpers syndrome.

Mutations:

SNPs:

E1143G, PNF

Age group:

infantile

Age of Onset: 0.2, Age of Patient: n/a, Age of Death: 2.5

Reference:

Ferrari et al, 2005;

[PubMed]

136

Description:

disease-free interval in the first 4 months after birth, followed by persistent vomiting, epileptic crises with loss of eye contact, and myoclonus in the upper limbs with secondary generalization and loss of consciousness. Persistent myoclonus in the upper limbs was associated with profound hypotonia and loss of eye contact. cortical atrophy and leukoencephalopathy in the subcortical areas of the frontal lobes. progressive hepatic failure with enlarged liver, hypoalbuminaemia and predominantly cholestatic jaundice led to the death of the child at 8 months of age.

Mutations:

SNPs:

E1143G, PNF

Age group:

infantile

Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 0.67

Reference:

Sarzi et al, 2007;

[PubMed]

137

Description:

Myoclonus, epilepsy, Psychomotor retardation, Alpers syndrome, steatosis

Mutations:

SNPs:

E1143G, PNF

Age group:

infantile

Age of Onset: 0.25, Age of Patient: n/a, Age of Death: n/a

Reference:

[PubMed]

138

Description:

Muscle weakness, respiratory failure, Alpers, Lactic acidosis, Seizures, Demential , developmental delay

Mutations:

SNPs:

E1143G, PNF

Age group:

childhood

Age of Onset: 4, Age of Patient: n/a, Age of Death: n/a

Reference:

Wolf et al, 2009;

[PubMed]

139

Description:

Alpers. At 7 months she developed focal clonic Status epilepticus. SE subsided slowly after a continuous infusion of valproic acid. she developed severe muscular hypotonia and feeding difficulties necessitating nasogastric feeding. Twelve weeks after disease onset, she was readmitted with vomiting and pneumonia. Infantile scoliosis.

Mutations:

Mousson de Camaret et al, 2011

SNPs:

PNF

Age group:

infantile

Age of Onset: 0.58, Age of Patient: n/a, Age of Death: 0.83

Reference:

[PubMed]

140

Description:

At 16 months of age, he started a severe status epilepticus. Cerebral MRI showed brain cortical atrophy. he developed intractable epileptic encephalopathy associated with generalized hypotonia and cortical blindness. diffuse hypotonia, lethargy and vomiting. During the two following years, epilepsy was always very active including spasms and myoclonic jerks. progressive hepatic failure. Alpers.

Mutations:

SNPs:

E1143G, PNF

Age group:

infantile

Age of Onset: 1.33, Age of Patient: n/a, Age of Death: 4.17

Reference:

[PubMed]

141

Description:

R-EPC (refractory epilepsia partialis continua), delayed psychomotor development. Has unrelated healthy parents. Pregnancy and birth were unremarkable. She had had a moderately delayed psychomotor development with sitting posture at 9 months of age and walking at 20 months of age. At 3 years old, she presented with acute partial status epilepticus. After this first episode, she developed refractory EPC with neurological regression leading to a severe encephalopathy. At 4 years, she was unable to hold her head up or to sit and had poor contact. Muscle biopsy showed lipid accumulation and spectrophotometric measurements of the indivi- dual RC complexes revealed CIII deficiency, associated with decreased activitiy of complexes II and V. In the liver, specific activity of complexes I, III and V was also affected. mtDNA depletion was identified by qPCR (25% of the mean normal control amount of mtDNA relative to nuclear DNA in the muscle and 30% in the liver). Sequencing identified only one heterozygous mutation (p.Trp748Ser) in POLG, inherited from the mother.

Mutations:

SNPs:

PNF

Age group:

infantile

Age of Onset: 2, Age of Patient: 4, Age of Death: n/a

Reference:

Kaliszewska et al, 2015;

[PubMed]

142

Description:

a psychomotor retardation and muscle hypotonia were observed since 2 months of age, and autistic behaviour was observed during early childhood. At the age of 3 years, the patient was given valproic acid due to episodes of unconsciousness and abnormal EEG pattern and responded suddenly with an acute liver failure.

Mutations:

PNF, W748S

Age group:

infantile

Age of Onset: 1.67, Age of Patient: n/a, Age of Death: 3.5

Reference:

[PubMed]

143

Description:

mtDNA depletion in muscle, Epilepsy, hepatopathy, movement disorder

Mutations:

T914P, W748S

Age group:

infantile

Age of Onset: 1.1, Age of Patient: n/a, Age of Death: n/a

Reference:

[PubMed]

144

Description:

reported as Alpers, onset at 4 years, presenting encephalopathy with epilepsy, hepatopathy, and movement disorder (ataxia). 15% mtDNA copy number in liver.

Mutations:

T914P, W748S

Age group:

childhood

Age of Onset: 4, Age of Patient: n/a, Age of Death: n/a

Reference:

Isohanni et al, 2011;

[PubMed]

145

Description:

developmental delay, vomiting, partial status epilepticus, epilepsia partialis continua, myoclonus, ataxia, alive at age 3.

Mutations:

T914P, W748S

SNPs:

E1143G

Age group:

infantile

Age of Onset: 2.5, Age of Patient: 3, Age of Death: n/a

Reference:

[PubMed]

146

Description:

Age 0.8, developmental delay, hypotonia, myoclinic seizures, spasticity, dystonia, exercise intolerance, GI reflux, abnormal EEG, elevated transaminases, increased signal basal ganglia, abnormal MRI, lactic acidosis, high CSF lactate.

Mutations:

T914P, W748S

Age group:

infantile

Age of Onset: n/a, Age of Patient: 0.8, Age of Death: n/a

Reference:

[PubMed]

147

Description:

Seizures. 98% mtDNA copy number in blood.

Mutations:

T914P, W748S

Age group:

childhood

Age of Onset: n/a, Age of Patient: 5, Age of Death: n/a

Reference:

Hinnell et al, 2012;

[PubMed]

148

Description:

Presented with generalized epilepsy and mild long-standing learning difficulties requiring special education, developed liver failure after taking valproate, migraines, right-sided epilepsia partialis continua, myoclonic arm jerks, a pancerebellar syndrome, and progressive cognitive impairment. mild external ophthalmoplegia, saccadic pursuit, writhing tongue movements, dysarthria, bilateral dysdiadochokinesis and dysmetria, mild sensory axonal peripheral neuropathy, ptosis

Mutations:

T914P, W748S

Age group:

juvenile

Age of Onset: 15, Age of Patient: n/a, Age of Death: n/a

Reference:

[PubMed]

149

Description:

Refractory generalized epilepsy with status epilepticus, hepatic cholestasis and cytolysis, proximal tubulopathy, hyperintensity of thalamus. mtDNA depletion.

Mutations:

T914P, W748S

Age group:

childhood

Age of Onset: 6, Age of Patient: n/a, Age of Death: n/a

Reference:

[PubMed]

150

Description:

reported as Alpers, onset at 1 years, presenting encephalopathy with epilepsy, hepatopathy, and movement disorder (ataxia). 32% mtDNA copy number in liver.

Mutations:

SNPs:

G11D

Age group:

infantile

Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a

Reference:

Stewart et al, 2009;

[PubMed]

151

Description:

Alpers, Seizures, Epilepsia partialis continua, liver failure, stroke-like episode.

Mutations:

SNPs:

E1143G, G11D

Age group:

infantile

Age of Onset: 1.33, Age of Patient: n/a, Age of Death: n/a

Reference:

Naess et al, 2009;

[PubMed]

152

Description:

Developmental retardation, Hypotonia, ataxia, seizures myoclonus, abnormal eye movement, gastrointestinal problems, hepatic involvement

Mutations:

SNPs:

G11D

Age group:

infantile

Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 1.1

Reference:

Vasta et al, 2012;

[PubMed]

153

Description:

PEO, alpers disease, ataxia, seizure, hypotonia, developemental delay,

Mutations:

SNPs:

E1143G, G11D

Age group:

infantile

Age of Onset: 0.001, Age of Patient: n/a, Age of Death: n/a

Reference:

Sofou et al, 2013;

[PubMed]

154

Description:

Alpers/ Alpers–Huttenlocher.

Mutations:

Q497H, R852C, W748S

SNPs:

E1143G

Age group:

infantile

Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a

Reference:

Tzoulis et al, 2009;

[PubMed]

155

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:

YlÃ¶nen et al, 2013;

[PubMed]

156

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:

[PubMed]

157

Description:

Peripheral neuropathy, CPEO, ptosis, COX deficiency, ragged red fibers, headaches/migraines, diarrhoea, lactic acidosis, hypotonia, ataxia, myoclonic seizures, exercise intolerance, muscle weakness, muscle cramps after exercise, optic atrophy, easy fatigability. 61% mtDNA copy number in muscle, 61% mtDNA copy number in blood.

Mutations:

R953C, W748S

Age group:

adult

Age of Onset: n/a, Age of Patient: 51, Age of Death: n/a

Reference:

Tang et al, 2012;

[PubMed]

158

Description:

Exercise intolerance, muscle weakness, persistent diarrhea, intermittent vomiting, bilateral ptosis, cognitive impairment with poor recall and expressive language difficulty, proximal myopathy, axonal sensorimotor peripheral neuropathy

Mutations:

R953C, W748S

Age group:

adult

Age of Onset: n/a, Age of Patient: 50, Age of Death: n/a

Reference:

Nolte et al, 2013;

[PubMed]

159

Description:

Generalized tonic-clonic seizures which, within 3 days, evolved to epilepsia partialis continua (EPC) with continuous left-sided myoclonic jerks. Multifocal brain lesions and global brain atrophy.

Mutations:

R627W, W748S

Age group:

juvenile

Age of Onset: 13, Age of Patient: 16, Age of Death: 17

Reference:

Nolte et al, 2013;

[PubMed]

160

Description:

This previously healthy 17-year-old patient developed repeated complex partial seizures starting with visual sensations, as well as myoclonic jerks of her right arm that rapidly evolved to generalized tonic-clonic seizures. Repeated complex partial seizures and considerable mental impairment.

Mutations:

R627W, W748S

Age group:

juvenile

Age of Onset: 17, Age of Patient: 17, Age of Death: n/a

Reference:

Simonati et al, 2003b;

[PubMed]

161

Description:

epilepsia partialis continua at 10 months, pyramido-cerebellar syndrome 19 months, myoclonic seizures when 4.5 years old. myoclonic jerks. At the age of 8 years, a brain CT scan showed atrophy of the right occipital cortex. signs and symptoms of liver dysfunction. chronic progressive liver disease. diffuse cortical atrophy. myoclonic epilepsy became resistant to any medication, myoclonic status along with episodes of respiratory failure. His clinical condition rapidly worsened and led to a vegetative state.

Mutations:

L244P, W748S

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.8, Age of Patient: 9, Age of Death: 15

Reference:

Simonati et al, 2003b;

[PubMed]

162

Description:

myoclonic fits of the right limbs and then a dystonic-ataxic syndrome at the age of 5 months. He had a rapid clinical deterioration. At age 6 months, a brain CT scan showed diffuse cortical atrophy. acute hepatic failure.

Mutations:

L244P, W748S

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.42, Age of Patient: n/a, Age of Death: 1.1

Reference:

Naimi et al, 2006;

[PubMed]

163

Description:

SCAE, age of onset 20, death at 27, ptosis and multiple deletions in muscle.

Mutations:

L304R, W748S

SNPs:

E1143G

Age group:

adult

Age of Onset: 20, Age of Patient: n/a, Age of Death: 27

Reference:

[PubMed]

164

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:

Isohanni et al, 2011;

[PubMed]

165

Description:

epilepsy, vomiting, lowered consciousness, partial status epilepticus, epilepsia partialis continua, myoclonus, pschomotor regression, liver failure before valproate treatment, death via pneumonia. 72-76% mtDNA copy number in muscle.

Mutations:

R807C, W748S

SNPs:

E1143G

Age group:

infantile

Age of Onset: 1, Age of Patient: n/a, Age of Death: 3

Reference:

Spinazzola et al, 2009;

[PubMed]

166

Description:

Onset of Alpers at 3 months, death at 19 months. Bilateral lesions of thalami.

Mutations:

D930N, W748S

Age group:

infantile

Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 1.5

Reference:

[PubMed]

167

Description:

Alpers. 46% mtDNA copy number in blood.

Mutations:

R852H, W748S

Age group:

childhood

Age of Onset: n/a, Age of Patient: 3, Age of Death: n/a

Reference:

Taanman et al, 2009;

[PubMed]

168

Description:

Hypotonia at 8 weeks, seizures, hepatopathy, lactic acidemia, died of liver failure. 9% mtDNA copy number in muscle, 11% mtDNA copy number in liver.

Mutations:

H1110Y, W748S

SNPs:

E1143G, Q1236H

Age group:

infantile

Age of Onset: 0.1, Age of Patient: n/a, Age of Death: 0.8

Reference:

[PubMed]

169

Description:

Seizures, ptosis, hepatic failure, ketosis, lactic acidosis, organic aciduria/tiglyglycine, elevated pyruvate, microcephaly, abnormal MRI. 33% mtDNA copy number in muscle, 46% mtDNA copy number in blood, ETC low.

Mutations:

G888D, W748S

Age group:

infantile

Age of Onset: n/a, Age of Patient: 2, Age of Death: n/a

Reference:

Tzoulis et al, 2009;

[PubMed]

170

Description:

PEO. Primary hypothyroidism and bilateral hearing loss of uncertain duration. She had been operated for bilateral ptosis at 75 years of age and presented to us with 2–3 years of worsening diplopia, gait unsteadiness and paresthaesiae in the distal lower limbs. asymmetrical ptosis and nearly complete external ophthalmoplegia with loss of convergence, oculocephalic reflex and Bell\'s reflex. She had symmetrical distal sensory loss in the lower limbs and absence of Achilles reflexes.

Mutations:

G737R, W748S

Age group:

adult

Age of Onset: 75, Age of Patient: 86, Age of Death: n/a

Reference:

Zsurka et al, 2008;

[PubMed]

171

Description:

Epilepsy, seizures, VPA induced liver failure.

Mutations:

L752P, W748S

SNPs:

E1143G

Age group:

childhood

Age of Onset: 7, Age of Patient: n/a, Age of Death: 10

Reference:

Kurt et al, 2010;

[PubMed]

172

Description:

Psychomotor delay, status epilepticus, liver disease, lactic acidosis, ADHD, mental retardation.

Mutations:

P1073L, W748S

Age group:

infantile

Age of Onset: 0.01, Age of Patient: n/a, Age of Death: 13

Reference:

[PubMed]

173

Description:

Alpers, age of onset 6 months, age of death 13 months. 41% mtDNA copy number. During the first 6 months of life, he was considered healthy, but was irritable with colic-like symptoms. failure to thrive, delayed motor development. myoclonus. leftsided hemiparesis.

Mutations:

R232H, W748S

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 1.08

Reference:

Komulainen et al, 2010;

[PubMed]

174

Description:

mental retardation, psychiatric symptoms, mild bilateral ptosis and epilepsy, Seizures occurred at age 11 years, and focal generalized epilepsy was diagnosed.

Mutations:

SNPs:

E1143G, R722H

Age group:

childhood

Age of Onset: 11, Age of Patient: 22, Age of Death: n/a

Reference:

[PubMed]

175

Description:

CPEO, Ptosis, Peripheral neuropathy, COX-deficient fibers, ragged red fibers, presence of mitochondrial dna deletions in muscle, epilepsy, Severe sensory and moderate motor neuronopathy, Distal neurogenic change, proximal myopathy

Mutations:

R1096C, W748S

Age group:

adult

Age of Onset: 25, Age of Patient: 49, Age of Death: n/a

Reference:

[PubMed]

176

Description:

Ragged Red Fibers, COX-Deficient Fibers. mtDNA depletion. He was healthy and his development was normal until 5 months of age. He developed failure to thrive and muscular hypotonia. At 4 years of age, he developed myoclonus, which was first limited to the right eye and the right side of the mouth, but then progressed to epilepsia partialis continua of the entire left side of the body without loss of consciousness. He has developed a complex movement disorder and cognitive impairment, but contact, speech, and memory functions have been retained. He also had ptosis and uncontrolled and uncoordinated movements, especially in his arms.

Mutations:

E1163G, W748S

SNPs:

E1143G

Age group:

infantile

Age of Onset: 0.417, Age of Patient: n/a, Age of Death: n/a

Reference:

YlÃ¶nen et al, 2013;

[PubMed]

177

Description:

late-onset parkinsons. Tremor. Cardiac arrhythmia.

Mutations: