Mitochondrial Dna Depletion Syndrome 7

Categories: Genetic diseases, Rare diseases, Liver diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 7

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 7:

Name: Mitochondrial Dna Depletion Syndrome 7 53 12 71 28 13 14
Ohaha Syndrome 53 12 49 24 55 71
Iosca 53 23 49 24 55 71
Infantile Onset Spinocerebellar Ataxia 12 49 55 14 69
Ophthalmoplegia-Hypotonia-Ataxia-Hypoacusis-Athetosis Syndrome 49 55
Ophthalmoplegia, Hypotonia, Ataxia, Hypacusis, and Athetosis 49 24
Spinocerebellar Ataxia Infantile with Sensory Neuropathy 49 71
Infantile-Onset Spinocerebellar Ataxia 23 24
Spinocerebellar Ataxia 8 71 69
Mtdps7 53 71
Ophthalmoplegia, Hypotonia, Ataxia, Hypoacusis, and Athetosis 53
Ophthalmoplegia - Hypotonia - Ataxia - Hypoacusis - Athetosis 49
Spinocerebellar Ataxia, Infantile, with Sensory Neuropathy 53
Mitochondrial Dna Depletion Syndrome 7 Hepatocerebral Type 71
Ophthalmoplegia Hypotonia Ataxia Hypoacusis and Athetosis 71
Spinocerebellar Ataxia 8, Formerly; Sca8, Formerly 53
Spinocerebellar Ataxia, Infantile-Onset; Iosca 53
Pure Spinocerebellar Ataxia Japanese Type 71
Spinocerebellar Ataxia, Infantile-Onset 53
Spinocerebellar Ataxia Infantile-Onset 71
Spinocerebellar Ataxia 8, Formerly 53
Sca4 Pure Japanese Type 71
Sca8, Formerly 53
Sca8 71


Orphanet epidemiological data:

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;


autosomal recessive

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


mitochondrial dna depletion syndrome 7:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Penetrance Penetrance is complete in both homozygotes and compound heterozygotes...


Summaries for Mitochondrial Dna Depletion Syndrome 7

NIH Rare Diseases : 49 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. Last updated: 4/9/2009

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, ophthalmoplegia and hearing impairment. An important gene associated with Mitochondrial Dna Depletion Syndrome 7 is TWNK (Twinkle MtDNA Helicase). Affiliated tissues include brain, liver and testes.

OMIM : 53 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 : 71 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.

Genetics Home Reference : 24 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.

GeneReviews: NBK3795

Related Diseases for Mitochondrial Dna Depletion Syndrome 7

Graphical network of the top 20 diseases related to Mitochondrial Dna Depletion Syndrome 7:

Diseases related to Mitochondrial Dna Depletion Syndrome 7

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 7

Symptoms via clinical synopsis from OMIM:

Neurologic Central Nervous System:
cerebellar atrophy
status epilepticus
Head And Neck Eyes:
optic atrophy
poor eye contact
abnormal eye movements

Neurologic Behavioral Psychiatric Manifestations:
mood disorders
uncontrolled rage

Abdomen Liver:
mitochondrial dna depletion

Endocrine Features:
hypergonadotrophic hypogonadism (in females in adolescence)

Muscle Soft Tissue:
muscle weakness
decreased complex i activity (rare)

Neurologic Peripheral Nervous System:
sensory axonal neuropathy
loss of deep tendon reflexes

Head And Neck Ears:
loss of vestibular caloric response

Genitourinary Internal Genitalia Female:
hypergonadotrophic hypogonadism (in females in adolescence)

Laboratory Abnormalities:
abnormal liver enzymes (rare)

Clinical features from OMIM:


Human phenotypes related to Mitochondrial Dna Depletion Syndrome 7:

55 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 ophthalmoplegia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000602
3 hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000365
4 optic atrophy 55 31 hallmark (90%) Very frequent (99-80%) HP:0000648
5 abnormality of movement 55 31 hallmark (90%) Very frequent (99-80%) HP:0100022
6 reduced tendon reflexes 55 31 hallmark (90%) Very frequent (99-80%) HP:0001315
7 abnormality of the autonomic nervous system 55 31 hallmark (90%) Very frequent (99-80%) HP:0002270
8 clumsiness 31 HP:0002312
9 muscle weakness 31 HP:0001324
10 athetosis 31 HP:0002305
11 excessive daytime somnolence 31 HP:0001262
12 nystagmus 31 HP:0000639
13 intellectual disability 31 HP:0001249
14 specific learning disability 31 HP:0001328
15 elevated hepatic transaminases 31 occasional (7.5%) HP:0002910
16 sensory axonal neuropathy 31 HP:0003390
17 migraine 31 HP:0002076
18 cerebral cortical atrophy 31 HP:0002120
19 psychosis 31 HP:0000709
20 hypergonadotropic hypogonadism 31 HP:0000815
21 areflexia 31 HP:0001284
22 cerebellar atrophy 31 HP:0001272
23 generalized hypotonia 31 HP:0001290
24 epileptic encephalopathy 31 HP:0200134
25 atrophy/degeneration affecting the brainstem 31 HP:0007366
26 poor eye contact 31 HP:0000817
27 loss of ability to walk 31 HP:0006957
28 epilepsia partialis continua 31 HP:0012847

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 7:

clumsiness, muscle weakness, ophthalmoplegia, athetosis, ataxia, abnormal pyramidal signs, tremor, muscle spasticity

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 7

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

Genetic Tests for Mitochondrial Dna Depletion Syndrome 7

Genetic tests related to Mitochondrial Dna Depletion Syndrome 7:

# Genetic test Affiliating Genes
1 Mitochondrial Dna Depletion Syndrome 7 (hepatocerebral Type) 28 TWNK

Anatomical Context for Mitochondrial Dna Depletion Syndrome 7

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 7:

Brain, Liver, Testes, Spinal Cord, Cerebellum, Eye

Publications for Mitochondrial Dna Depletion Syndrome 7

Articles related to Mitochondrial Dna Depletion Syndrome 7:

(show all 19)
# Title Authors Year
Sporadic infantile-onset spinocerebellar ataxia caused by missense mutations of the inositol 1,4,5-triphosphate receptor type 1 gene. ( 25794864 )
Infantile Onset Spinocerebellar Ataxia 2 (SCA2): A Clinical Report With Review of Previous Cases. ( 24300164 )
Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy. ( 24816431 )
Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2. ( 23047744 )
Case of infantile onset spinocerebellar ataxia type 5. ( 22914369 )
Identification of a novel Twinkle mutation in a family with infantile onset spinocerebellar ataxia by whole exome sequencing. ( 22353293 )
Novel Autosomal Recessive c10orf2 Mutations Causing Infantile-Onset Spinocerebellar Ataxia. ( 22928142 )
Infantile-onset spinocerebellar ataxia and mitochondrial recessive ataxia syndrome are associated with neuronal complex I defect and mtDNA depletion. ( 18775955 )
Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. ( 16135556 )
cDNA cloning, expression profile and genomic structure of a novel human transcript on chromosome 10q24, and its analyses as a candidate gene for infantile onset spinocerebellar ataxia. ( 12459258 )
Infantile onset spinocerebellar ataxia with sensory neuropathy (IOSCA): neuropathological features. ( 9879682 )
Toward cloning of a novel ataxia gene: refined assignment and physical map of the IOSCA locus (SCA8) on 10q24. ( 9027505 )
Tracing an ancestral mutation: genealogical and haplotype analysis of the infantile onset spinocerebellar ataxia locus. ( 8889554 )
Infantile-onset spinocerebellar ataxia: MR and CT findings. ( 7484627 )
Primary hypogonadism in females with infantile onset spinocerebellar ataxia. ( 8552218 )
Sensory neuropathy in infantile onset spinocerebellar ataxia (IOSCA). ( 8159181 )
Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease. ( 8133312 )
Infantile onset spinocerebellar ataxia represents an allelic disease distinct from other hereditary ataxias. ( 7877879 )
Infantile-Onset Spinocerebellar Ataxia ( 20301746 )

Variations for Mitochondrial Dna Depletion Syndrome 7

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 7:

# Symbol AA change Variation ID SNP ID
1 TWNK p.Thr457Ile VAR_039045 rs80356544
2 TWNK p.Tyr508Cys VAR_043797 rs80356540
3 TWNK p.Ala318Thr VAR_065104 rs80356542
4 TWNK p.Leu360Gly VAR_065107
5 TWNK p.Leu456Val VAR_067722 rs386834145

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 7:

# Gene Variation Type Significance SNP ID Assembly Location
1 TWNK NM_021830.4(TWNK): c.1287C> T (p.Ala429=) single nucleotide variant Pathogenic rs80356541 GRCh37 Chromosome 10, 102749444: 102749444
2 TWNK NM_021830.4(TWNK): c.1387C> T (p.Arg463Trp) single nucleotide variant Likely pathogenic rs386834146 GRCh37 Chromosome 10, 102749544: 102749544
3 ATXN8; ATXN8OS NR_002717.2(ATXN8OS): n.1103_1105CTG(15_40) NT expansion Pathogenic,risk factor rs193922930 GRCh37 Chromosome 13, 70713516: 70713518
4 TWNK NM_021830.4(TWNK): c.1370C> T (p.Thr457Ile) single nucleotide variant Pathogenic rs80356544 GRCh37 Chromosome 10, 102749527: 102749527
5 TWNK NM_021830.4(TWNK): c.1523A> G (p.Tyr508Cys) single nucleotide variant Pathogenic rs80356540 GRCh37 Chromosome 10, 102750231: 102750231
6 TWNK NM_021830.4(TWNK): c.952G> A (p.Ala318Thr) single nucleotide variant Pathogenic rs80356542 GRCh37 Chromosome 10, 102748919: 102748919
7 TWNK NM_021830.4(TWNK): c.333delT (p.Leu112Serfs) deletion Pathogenic rs886037832 GRCh37 Chromosome 10, 102748300: 102748300
8 TWNK NM_021830.4(TWNK): c.904C> T (p.Arg302Trp) single nucleotide variant Likely pathogenic rs374997012 GRCh37 Chromosome 10, 102748871: 102748871

Expression for Mitochondrial Dna Depletion Syndrome 7

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

Pathways for Mitochondrial Dna Depletion Syndrome 7

GO Terms for Mitochondrial Dna Depletion Syndrome 7

Cellular components related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.02 ATCAY MRPL43 SACS SLC25A4 TWNK

Sources for Mitochondrial Dna Depletion Syndrome 7

9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
51 Novoseek
54 OMIM via Orphanet
58 PubMed
66 SNOMED-CT via Orphanet
68 Tocris
70 UMLS via Orphanet
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