MTDPS7
MCID: MTC054
MIFTS: 51
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Mitochondrial Dna Depletion Syndrome 7 (MTDPS7)
Categories:
Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases
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MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 7:
Characteristics:Orphanet epidemiological data:58
infantile-onset spinocerebellar ataxia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: adolescent,early childhood,infantile,late childhood,young Adult; OMIM:56
Inheritance:
autosomal recessive
Miscellaneous:
progressive disorder onset 6 to 18 months some features occur in adolescence, including migraine, seizures, and psychiatric disorders severe epilepsy may lead to early death carrier frequency in finland is 1 in 230 HPO:31
mitochondrial dna depletion syndrome 7:
Inheritance autosomal recessive inheritance Onset and clinical course progressive Classifications:
MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases Anatomical: Neuronal diseases Liver diseases Eye diseases Gastrointestinal diseases Bone diseases Nephrological diseases Ear diseases Cardiovascular diseases
ICD10:
33
Orphanet: 58
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NIH Rare Diseases :
52
The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1186 Definition Infantile-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. Epidemiology So far, 24 cases have been reported. In Finland, IOSCA has a population carrier frequency of more than 1:230. Clinical description IOSCA 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. Etiology IOSCA 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 methods The 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 diagnosis Differential 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 diagnosis Prenatal testing may be available for families in which the disease-causing mutations have already been identified. Genetic counseling IOSCA 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 treatment IOSCA 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. Prognosis Prognosis 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 polyneuropathy and friedreich ataxia, and has symptoms including muscle weakness, ataxia and tremor. An important gene associated with Mitochondrial Dna Depletion Syndrome 7 is TWNK (Twinkle MtDNA Helicase), and among its related pathways/superpathways are Mitochondrial Gene Expression and Nucleotide Metabolism. Affiliated tissues include brain, liver and eye, and related phenotypes are hearing impairment and optic atrophy Disease Ontology : 12 A mitochondrial DNA depletion syndrome 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. People with IOSCA often develop problems with the autonomic nervous system, which controls involuntary body functions. As a result, they may experience excessive sweating, difficulty controlling urination, and severe constipation. IOSCA also leads to vision and hearing problems that begin by about age 7. Children with this disorder develop weakness in the muscles that control eye movement (ophthalmoplegia). In their teenage years they experience degeneration of the nerves that carry information from the eyes to the brain (optic atrophy), which can result in vision loss. Hearing loss caused by nerve damage (sensorineural hearing loss) typically occurs during childhood and progresses to profound deafness. Individuals with IOSCA may have recurrent seizures (epilepsy). These seizures can lead to severe brain dysfunction (encephalopathy). Most people with IOSCA survive into adulthood. However, a few individuals with IOSCA have an especially severe form of the disorder involving liver damage and encephalopathy that develops during early childhood. These children do not generally live past age 5. OMIM : 56 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 : 73 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
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Human phenotypes related to Mitochondrial Dna Depletion Syndrome 7:58 31 (show all 31)
Symptoms via clinical synopsis from OMIM:56Clinical features from OMIM:271245UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 7:muscle weakness, ataxia, tremor, ophthalmoplegia, clumsiness, athetosis, muscle spasticity, abnormal pyramidal signs |
Cochrane evidence based reviews: infantile onset spinocerebellar ataxia |
MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 7:40
Brain,
Liver,
Eye,
Cerebellum,
Spinal Cord,
Testes
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Articles related to Mitochondrial Dna Depletion Syndrome 7:(show all 33)
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ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 7:6 (show top 50) (show all 85)
UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 7:73
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Cellular components related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:
Biological processes related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:
Molecular functions related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:
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