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Disease Profile

Ataxia with oculomotor apraxia type 1

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

G11.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

EAOH; Ataxia-oculomotor apraxia 1; AOA1;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 1168

Definition
A rare autosomal recessive cerebellar ataxia, characterized by progressive cerebellar ataxia associated with oculomotor apraxia, severe neuropathy, and hypoalbuminemia.

Epidemiology
Ataxia-oculomotor apraxia type 1 (AOA1) represents 3.6% of all autosomal recessive cerebellar ataxia (ARCA) in Portugal; in Japan, AOA1 seems to be the most frequent cause of ARCA. In a cohort of 227 patients mostly of French origin with progressive cerebellar ataxia selected after exclusion of Friedreich ataxia, the relative frequency of AOA1 was of 5%.

Clinical description
Cerebellar ataxia is the first manifestation of AOA1 with a mean age of onset of 4.3 years (2-10 years) and is characterized by progressive gait imbalance followed by dysarthria, and limb dysmetria. Later, peripheral axonal motor neuropathy dominates the clinical picture. Oculomotor apraxia (OMA; inability to coordinate eyes ± head movements: when the head turns toward a lateral target; the head reaches the target before the eyes) is present in almost all individuals with AOA1. Chorea is present at onset in 80% of patients and upper limb dystonia (see this term) occurs in about 50% of individuals. Additional features include square wave jerks, saccadic pursuit and gaze-evoked nystagmus, areflexia followed by severe peripheral neuropathy. Variable intellectual disability is observed.

Etiology
AOA1 results from mutations in APTX gene (9p13.3) encoding aprataxin which plays a role in DNA-single-strand break repair. Most mutations identified so far are localized in exons 5, 6 and 7. Some correlations between genotype and phenotype have been established: for example severe and persistent choreic phenotype is associated with mutations A198V; truncating mutations are associated with earlier onset and deletions with more severe phenotype and intellectual disability.

Diagnostic methods
Diagnosis of AOA1 is based on the clinical features, the progressive evolution, the absence of extraneurologic findings and family history. Electromyography findings reveal severe axonal sensory-motor neuropathy. Oculographic recordings demonstrate normal latencies, hypometric saccades, decrease mean gain in amplitude and broken saccades into multiple successive saccades. Cerebral magnetic resonance imagery displays cerebellar atrophy. Hypoalbuminemia and hypercholesterolemia are usual (disease duration is positively correlated with cholesterol and negatively correlated with albumin levels). Diagnosis is confirmed by molecular analysis of APTX gene.

Differential diagnosis
Differential diagnosis includes Friedreich ataxia, ataxia with vitamin E deficiency, AOA2, ataxia-telangiectasia, ataxia-telangiectasia-like disorder, autosomal recessive spastic ataxia of Charlevoix-Saguenay (see these terms).

Antenatal diagnosis
Carrier testing for at-risk family members and prenatal testing are possible if both disease-causing alleles in a family are known.

Genetic counseling
Transmission of AOA1 is autosomal recessive. Genetic counseling is recommended as each sib of an affected individual has 25% chance of being affected, 50% chance of being an asymptomatic carrier, and 25% chance of being neither affected nor a carrier.

Management and treatment
No specific treatment exists for AOA1 and management is mainly supportive. It includes physical therapy for cerebellar ataxia and disabilities resulting from peripheral neuropathy; educational support for reading and writing difficulties, speech therapy for dysarthria and cognitive impairment. Low-cholesterol diet and hypolipemiant treatment are recommended. Routine follow-up with a neurologist or neurogenetician is suggested. Some therapeutic trials are on the way such as the evaluation of efficacy of Coenzyme Q10 in evolution of the disease.

Prognosis
AOA1 is a progressive neurodegenerative disorder and most patients usually become wheelchair bound from seven to ten years after onset of the disease.

Visit the Orphanet disease page for more resources.

Symptoms

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.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Ataxia
0001251
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Medial flaring of the eyebrow
0010747
Peripheral neuropathy
0009830
5%-29% of people have these symptoms
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
1%-4% of people have these symptoms
Choreoathetosis
0001266
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Areflexia
Absent tendon reflexes
0001284
Autosomal recessive inheritance
0000007
Axonal degeneration
0040078
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Decreased number of large peripheral myelinated nerve fibers
0003387
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Distal amyotrophy
Distal muscle wasting
0003693
Distal sensory impairment
Decreased sensation in extremities
0002936
Dysarthria
Difficulty articulating speech
0001260
Dystonia
0001332
Gait ataxia
Inability to coordinate movements when walking
0002066
Gaze-evoked nystagmus
0000640
Hypercholesterolemia
Elevated serum cholesterol
Elevated total cholesterol
Increased total cholesterol

[ more ]

0003124
Hypoalbuminemia
Low blood albumin
0003073
Hypometric saccades
0000571
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Limb ataxia
0002070
Muscle weakness
Muscular weakness
0001324
Oculomotor apraxia
0000657
Peripheral axonal degeneration
0000764
Pes cavus
High-arched foot
0001761
Progressive external ophthalmoplegia
0000590
Scoliosis
0002650
Tremor
0001337
Truncal ataxia
Instability or lack of coordination of central trunk muscles
0002078

Organizations

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

    Learn more

    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

    • 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 Ataxia with oculomotor apraxia type 1. Click on the link to view a sample search on this topic.