Rare Ophthalmology News

Disease Profile

Hypomyelination with atrophy of basal ganglia and cerebellum

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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

E75.2

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.

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)

H-ABC; Leukodystrophy, hypomyelinating, 6; HLD6;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) is a disease that affects certain parts of the brain. Symptoms usually begin in infancy or early childhood and worsen over time. Severity of symptoms and rate of progression can vary.[1] Symptoms may include delayed motor development, learning difficulties, upper-motor neuron dysfunction (spasticity, exaggerated reflexes, and Babinski signs), dystonia, rigidity, involuntary movements, and speech and swallowing problems.[1]

H-ABC is caused by a mutation in the TUBB4A gene. Inheritance is autosomal dominant, but most cases are due to a new mutation occurring for the first time in a person with the condition.[1][2]

Treatment may involve taking medications to ease symptoms, physical therapy, and surgery when dystonia does not improve with medication.[1]

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
5%-29% of people have these symptoms
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Percent of people who have these symptoms is not available through HPO
Ataxia
0001251
Autosomal dominant inheritance
0000006
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral hypomyelination
0006808
Choreoathetosis
0001266
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Dysarthria
Difficulty articulating speech
0001260
Dystonia
0001332
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Leukodystrophy
0002415
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Motor delay
0001270
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Optic atrophy
0000648
Poor speech
0002465
Progressive
Worsens with time
0003676
Rigidity
Muscle rigidity
0002063
Seizure
0001250
Short stature
Decreased body height
Small stature

[ more ]

0004322
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Specific learning disability
0001328
Sporadic
No previous family history
0003745
Tremor
0001337
Variable expressivity
0003828
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505

Cause

Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) is caused by a mutation in the TUBB4A gene. The mutation typically occurs for the first time in a person with the condition (i.e. it typically is not inherited from a parent).[2][1]

The TUBB4A gene is involved in the formation of microtubules. Microtubules are an important part of the cytoskeleton (which gives cells their shape). They also play important roles in many cellular processes such as cell division, motility, and transport. The TUBB4A gene is mostly expressed ("turned on") in the central nervous system (CNS), especially in parts of the brain affected by H-ABC. Mutations in this gene are thought to impair the formation or stability of microtubules. This in turn may impairs the structure or roles of cells in the CNS, leading to the signs and symptoms of H-ABC.[1]

Diagnosis

H-ABC is diagnosed based on the presence of characteristic symptoms, a magnetic resonance imaging (MRI) scan of the brain, and genetic testing confirming a mutation in the TUBB4A gene.[1]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Unfortunately, there is currently no cure for hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC). However, quality of life may be improved with management of individual symptoms of the condition, which may involve:

    • Medications and physical therapy for spasticity (e.g. baclofen, diazepam or intramuscular botulinum toxin)
    • Medications for dystonia (e.g. trihexyphenidyl, tetrabenazine, or high doses of levodopa and carbidopa which were reportedly helpful in case reports)
    • Gastrostomy for feeding for swallowing dysfunction
    • Routine treatment for seizures, constipation, and gastroesophageal reflux disease

    Routine evaluations of swallowing and feeding, nutrition, orthopedic and joint integrity, and neurologic symptoms are recommended.[1]

    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

      Organizations Providing General Support

        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

        • 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 Hypomyelination with atrophy of basal ganglia and cerebellum. Click on the link to view a sample search on this topic.

          References

          1. Nahhas N, Conant A, Hamilton E, Curiel J, Simons C, van der Knaap M, Vanderver A. TUBB4A-Related Leukodystrophy. GeneReviews. November 3, 2016; https://www.ncbi.nlm.nih.gov/books/NBK395611/.
          2. Kniffin CL. Leukodystrophy, Hypomyelinating, 6; HLD6. OMIM. June 16, 2015; https://omim.org/entry/612438.

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