Mitochondrial Dna Depletion Syndrome 7 (MTDPS7)

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OMIM 57 271245 Disease Ontology 12 DOID:0080126 MeSH 44 C535523 D020754 Orphanet 59 ORPHA1186 ICD10 via Orphanet 34 G11.1

MESH via Orphanet 45 C535523 UMLS via Orphanet 74 C1849096 MedGen 42 C1849096 SNOMED-CT via HPO 69 258211005 103276001 15188001 343087000 95828007 16110005 563001 76976005 69322001 370999003 412786000 228156007 247578003 91138005 85102008 398151007 398152000 271782001 79519003 95646004 349006 37280007 81308009 26544005 37796009 278849000 230456007 44913001 58593005 7006003 166603001 166643006 75183008 252157006 255314001 241006 70375006 more UMLS 73 C1849096 C1837454

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1186Disease definitionInfantile-onset spinocerebellar ataxia (IOSCA) is a hereditary neurological disorder with early and severe involvement of both the peripheral and central nervous systems. It has only been described in Finnish families.EpidemiologySo far, 24 cases have been reported. In Finland, IOSCA has a population carrier frequency of more than 1:230.Clinical descriptionIOSCA is characterized by very early ataxia, athetosis and reduced tendon reflexes (between 9 and 18 months of age). Ophthalmoplegia and sensorineural hearing loss are diagnosed in childhood. Other features, such as optic atrophy and sensory neuropathy with progressive loss of myelinated fibers in the sural nerve, appear later in the disease course. Hypogonadism may occur in females. Some patients show intellectual deficit. Epilepsy is a late manifestation and seizures may be life-threatening.EtiologyIOSCA is caused by mutations in the C10orf2 gene (10q24) encoding the mitochondrial helicase Twinkle. The c.1523A>G (p.Y508C) causative mutation has been postulated to be a founder mutation. Twenty-one of the reported patients were homozygous for this mutation, and three were compound heterozygotes: c.952G>A/c.1523A>G (two patients) and c.1523A>G/c.1287C>T (one patient). The mutations lead to mtDNA depletion in the brain and the liver, but not in the muscle.Diagnostic methodsThe diagnosis is based on clinical and pathological findings. Studies of sural nerve biopsies reveal an early and rapidly progressive axonal neuropathy. Neuroimaging studies revealing cerebellar atrophy and genetic testing for the c.1523A>G mutation may also help to confirm the diagnosis.Differential diagnosisDifferential diagnoses include early-onset cerebellar ataxias with sensory axonal neuropathy and epileptic encephalopathy, mitochondrial disorders with axonal neuropathy (such as Friedreich ataxia), progressive external ophthalmoplegia (PEO), juvenile- or adult-onset mitochondrial recessive ataxia syndrome (MIRAS), and POLG-related disorders (see theseterms).Antenatal diagnosisPrenatal testing may be available for families in which the disease-causing mutations have already been identified.Genetic counselingIOSCA is inherited in an autosomal recessive manner. Genetic counseling is an important clinical tool for preventing new cases, especially for couples with an affected first child: the risk of having an affected child in further pregnancies is 25%.Management and treatmentIOSCA patients are often managed by a multidisciplinary team, involving a pediatrician, neurologist, psychiatrist, orthopedic surgeon, physical and occupational therapists, genetic counselor, and social worker. Treatment is symptomatic and may include: (1) hearing aids, speech therapy and sign language for deafness; (2) physical therapy, orthotic devices and orthopedic surgery for sensory axonal neuropathy; (3) walking aids, a wheelchair, physiotherapy and occupational therapy for ataxia; (4) antiepileptic drugs for seizures and (5) antipsychotics and antidepressants for psychiatric symptoms.PrognosisPrognosis is unfavorable. Patients are wheelchair-bound by adolescence. Early death is common due to severe seizures. The clinical course seems to be more rapid and severe (with death during infancy) in c.952G>A/ c.1523A>G compound heterozygotes.Visit the Orphanet disease page for more resources.

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 7, also known as ohaha syndrome, is related to spinocerebellar ataxia 8 and spinocerebellar ataxia 31, and has symptoms including ataxia, muscle weakness and tremor. An important gene associated with Mitochondrial Dna Depletion Syndrome 7 is TWNK (Twinkle MtDNA Helicase). Affiliated tissues include brain, liver and testes, and related phenotypes are ataxia and hearing impairment

Disease Ontology : ¹² A mitochondrial metabolism disease that is characterized by progressive ataxia, hypotonia, hyporeflexia, athetosis and sensory impairment and has material basis in autosomal recessive homozygous or compound heterozygous mutation in the C10ORF2 gene, which encodes the twinkle and twinky proteins, on chromosome 10q24.

Genetics Home Reference : ²⁵ Infantile-onset spinocerebellar ataxia (IOSCA) is a progressive disorder that affects the nervous system. Babies with IOSCA develop normally during the first year of life. During early childhood, however, they begin experiencing difficulty coordinating movements (ataxia); very weak muscle tone (hypotonia); involuntary writhing movements of the limbs (athetosis); and decreased reflexes. By their teenage years affected individuals require wheelchair assistance.

OMIM : ⁵⁷ Mitochondrial DNA depletion syndrome-7 is an autosomal recessive severe neurodegenerative disorder characterized primarily by hypotonia, ataxia, ophthalmoplegia, hearing loss, seizures, and sensory axonal neuropathy. Although originally classified as a form of spinocerebellar ataxia (see, e.g., SCA1, 164400) (Koskinen et al., 1994), it has been reclassified as a mitochondrial DNA depletion syndrome (Hakonen et al., 2008) based on the finding of mtDNA depletion in the brain and liver of affected individuals. For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (271245)

UniProtKB/Swiss-Prot : ⁷⁵ Mitochondrial DNA depletion syndrome 7: A severe disease associated with mitochondrial dysfunction. Some patients are affected by progressive atrophy of the cerebellum, brain stem, the spinal cord, and sensory axonal neuropathy. Clinical features include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural hearing deficit, sensory axonal neuropathy, epileptic encephalopathy and female hypogonadism. In some individuals liver dysfunction and multi-organ failure is present.

GeneReviews: NBK3795

Clinical features from OMIM:

271245

Search Clinical Trials , NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 7

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 7.