Recessive mitochondrial ataxia syndrome
General Information (adopted from Orphanet):
| Synonyms, Signs: |
MIRAS |
| Number of Symptoms | 32 |
| OrphanetNr: | 94125 |
| OMIM Id: |
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| ICD-10: |
G11.8 |
| UMLs: |
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| MeSH: |
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| MedDRA: |
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| Snomed: |
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Prevalence, inheritance and age of onset:
| Prevalence: | No data available. |
| Inheritance: |
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| Age of onset: |
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Disease classification (adopted from Orphanet):
| Parent Diseases: |
Ataxia neuropathy spectrum
-Rare developmental defect during embryogenesis -Rare genetic disease -Rare neurologic disease Autosomal recessive metabolic cerebellar ataxia -Rare eye disease -Rare genetic disease -Rare neurologic disease |
Comment:
| The clinical phenotypes of mitochondrial recessive ataxia syndrome (MIRAS) vary considerably and can be divided into three groups: 1) childhood-onset encephalopathy and hepatopathy, 2) juvenile-onset refractory epilepsy and migraine-like headaches, and 3) adult-onset ataxia and neuropathy with additional symptoms such as psychiatric symptoms and cognitive impairment (PMID:20695297). MIRAS is due to the mutations c.1399GNA (A467T) and c.2243GNC (W748S) of POLG1 (encoding the catalytic subunit of the mitochondrial DNA polymerase gamma), and is clinically characterized by early onset ataxia, variably associated with peripheral neuropathy, epilepsy, headache, cognitive impairment, psychiatric disturbances, movement disorders, and ophthalmoplegia. MIRAS is considered a common cause of inherited ataxia in Northern Europe (PMID:25586537). PMID:25586537 describes a new case of MIRAS with features of Friedreich's ataxia-like and co-occurrence of Brugada syndrome (BrS). PMID:22166854 describes a new case of MIRAS mimicking dominant spinocerebellar ataxia with the homozygous mutations c.2243GNC in cis with c.3428ANG causing W748S and E1143G amino acid changes in the polypeptide. It is ranging from 0.6% of the population in Belgium to 0.8% in Finland or 2% in Norway, but with limited amount or no patients in Italy and UK. MIRAS closely resembles IOSCA (Infantile-onset spinocerebellar ataxia), except for the later onset of 5 – 41 years in MIRAS compared to 1 – 2 years in IOSCA (PMID:18775955). |
Symptom Information:
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(HPO:0000613) | Photophobia | 22166854 | IBIS | 158 / 7739 | ||
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(HPO:0000651) | Diplopia | 22166854 | IBIS | 37 / 7739 | ||
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(HPO:0000602) | Ophthalmoplegia | 25586537 | IBIS | 56 / 7739 | ||
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(HPO:0010532) | Paroxysmal vertigo | 22166854 | IBIS | 1 / 7739 | ||
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(HPO:0000739) | Anxiety | 22166854 | IBIS | 67 / 7739 | ||
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(HPO:0002312) | Clumsiness | 22166854 | IBIS | 28 / 7739 | ||
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(HPO:0001298) | Encephalopathy | 20695297 | IBIS | 72 / 7739 | ||
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(HPO:0001271) | Polyneuropathy | 22166854 | IBIS | 56 / 7739 | ||
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(HPO:0001260) | Dysarthria | 22166854 | IBIS | 329 / 7739 | ||
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(HPO:0000708) | Behavioral abnormality | 25586537 | IBIS | 212 / 7739 | ||
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(HPO:0002315) | Headache | 25586537 | IBIS | 175 / 7739 | ||
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(HPO:0009830) | Peripheral neuropathy | 25586537 | IBIS | 206 / 7739 | ||
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(HPO:0001288) | Gait disturbance | 22166854 | IBIS | 318 / 7739 | ||
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(HPO:0100543) | Cognitive impairment | 25586537 | IBIS | 230 / 7739 | ||
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(HPO:0001250) | Seizures | 25586537 | IBIS | 1245 / 7739 | ||
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(HPO:0011096) | Peripheral demyelination | 22166854 | IBIS | 28 / 7739 | ||
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(HPO:0010534) | Transient global amnesia | 22166854 | IBIS | 1 / 7739 | ||
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(HPO:0000716) | Depression | 22166854 | IBIS | 99 / 7739 | ||
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(HPO:0001251) | Ataxia | 20695297 | IBIS | 413 / 7739 | ||
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(HPO:0003236) | Elevated serum creatine phosphokinase | 22166854 | IBIS | 214 / 7739 | ||
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(HPO:0012102) | Abnormal mitochondrial number | 22166854 | IBIS | 4 / 7739 | ||
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(HPO:0002090) | Pneumonia | 22166854 | IBIS | 59 / 7739 | ||
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(HPO:0002204) | Pulmonary embolism | 22166854 | IBIS | 26 / 7739 | ||
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(HPO:0003689) | Multiple mitochondrial DNA deletions | 18775955 | IBIS | 12 / 7739 | ||
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(MedDRA:10062938) | Mitochondrial hepatopathy | 20695297 | IBIS | 2 / 7739 | ||
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(HPO:0001317) | Abnormality of the cerebellum | 22166854 | IBIS | 36 / 7739 | ||
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(HPO:0002529) | Neuronal loss in central nervous system | 22166854 | IBIS | 37 / 7739 | ||
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(HPO:0006827) | Atrophy of the spinal cord | 22166854 | IBIS | 5 / 7739 | ||
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(OMIM) | Subsarcolemmal mitochondrial accumulation | 22166854 | IBIS | 4 / 7739 | ||
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(HPO:0007047) | Atrophy of the dentate nucleus | 22166854 | IBIS | 3 / 7739 | ||
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(HPO:0002500) | Abnormality of the cerebral white matter | 22166854 | IBIS | 73 / 7739 | ||
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(OMIM) | Epilepsy, refractory (onset in adolescence or young adulthood) | 20695297 | IBIS | 3 / 7739 |
Associated genes:
| POLG1; |
ClinVar (via SNiPA)
| Gene symbol | Variation | Clinical significance | Reference |
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