National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Infantile onset spinocerebellar ataxia


Other Names:
Ophthalmoplegia, hypotonia, ataxia, hypacusis, and athetosis; OHAHA syndrome; IOSCA; Ophthalmoplegia, hypotonia, ataxia, hypacusis, and athetosis; OHAHA syndrome; IOSCA; Spinocerebellar ataxia 8 (formerly); SCA8 (formerly); Spinocerebellar ataxia infantile with sensory neuropathy; Ophthalmoplegia - hypotonia - ataxia - hypoacusis - athetosis; Ophthalmoplegia-hypotonia-ataxia-hypoacusis-athetosis syndrome See More
Categories:
This disease is grouped under:
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

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.
Last updated: 4/1/2009

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the autonomic nervous system 0002270
Ataxia 0001251
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Ophthalmoplegia
Eye muscle paralysis
0000602
Optic atrophy 0000648
Reduced tendon reflexes 0001315
5%-29% of people have these symptoms
Elevated hepatic transaminase
High liver enzymes
0002910
Percent of people who have these symptoms is not available through HPO
Areflexia
Absent tendon reflexes
0001284
Athetosis
Involuntary writhing movements in fingers, hands, toes, and feet
0002305
Atrophy/Degeneration affecting the brainstem 0007366
Autosomal recessive inheritance 0000007
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Clumsiness 0002312
Encephalopathy 0001298
Epilepsia partialis continua 0012847
Epileptic encephalopathy 0200134
Excessive daytime somnolence
More than typical sleepiness during day
0001262
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Hypergonadotropic hypogonadism 0000815
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Loss of ability to walk 0006957
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches
[ more ] 		0002076
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Poor eye contact 0000817
Progressive
Worsens with time
0003676
Psychosis 0000709
Sensory axonal neuropathy 0003390
Specific learning disability 0001328
Status epilepticus
Repeated seizures without recovery between them
0002133
Showing of 32 |
Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

  • Coordination of Rare Diseases at Sanford (CoRDS) hosts a specific registry for patients with ataxia in partnership with the National Ataxia Foundation. The goal of the CoRDS registry is to connect as many patients and researchers as possible to help advance treatments and cures for rare diseases. The CoRDS registry is free for patients to enroll and for researchers to access.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Infantile onset spinocerebellar ataxia. Click on the link to view a sample search on this topic.

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