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Fatty acid hydroxylase-associated neurodegeneration
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Reviewed October 2012
What is fatty acid hydroxylase-associated neurodegeneration?
Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a progressive disorder of the nervous system (neurodegeneration) characterized by problems with movement and vision that begin during childhood or adolescence.
Changes in the way a person walks (gait) and frequent falls are usually the first noticeable signs of FAHN. Affected individuals gradually develop extreme muscle stiffness (spasticity) and exaggerated reflexes. They typically have involuntary muscle cramping (dystonia), problems with coordination and balance (ataxia), or both. The movement problems worsen over time, and some people with this condition eventually require wheelchair assistance.
People with FAHN often develop vision problems, which occur due to deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and difficulties with the muscles that control eye movement. Affected individuals may have a loss of sharp vision (reduced visual acuity), decreased field of vision, impaired color perception, eyes that do not look in the same direction (strabismus), rapid involuntary eye movements (nystagmus), or difficulty moving the eyes intentionally (supranuclear gaze palsy).
Speech impairment (dysarthria) also occurs in FAHN, and severely affected individuals may lose the ability to speak. People with this disorder may also have difficulty chewing or swallowing (dysphagia). In severe cases, they may develop malnutrition and require a feeding tube. The swallowing difficulties can lead to a bacterial lung infection called aspiration pneumonia, which can be life-threatening. As the disorder progresses, some affected individuals experience seizures and a decline in intellectual function.
Magnetic resonance imaging (MRI) of the brain in people with FAHN shows signs of iron accumulation, especially in an area of the brain called the globus pallidus, which is involved in regulating movement. Similar patterns of iron accumulation are seen in certain other neurological disorders such as infantile neuroaxonal dystrophy and pantothenate kinase-associated neurodegeneration. All these conditions belong to a class of disorders called neurodegeneration with brain iron accumulation (NBIA).
How common is fatty acid hydroxylase-associated neurodegeneration?
FAHN is a rare disorder; only a few dozen cases have been reported.
What genes are related to fatty acid hydroxylase-associated neurodegeneration?
Mutations in the FA2H gene cause FAHN. The FA2H gene provides instructions for making an enzyme called fatty acid 2-hydroxylase. This enzyme modifies fatty acids, which are building blocks used to make fats (lipids). Specifically, fatty acid 2-hydroxylase adds a single oxygen atom to a hydrogen atom at a particular point on a fatty acid to create a 2-hydroxylated fatty acid. Certain 2-hydroxylated fatty acids are important in forming normal myelin; myelin is the protective covering that insulates nerves and ensures the rapid transmission of nerve impulses. The part of the brain and spinal cord that contains myelin is called white matter.
The FA2H gene mutations that cause FAHN reduce or eliminate the function of the fatty acid 2-hydroxylase enzyme. Reduction of this enzyme's function may result in abnormal myelin that is prone to deterioration (demyelination), leading to a loss of white matter (leukodystrophy). Leukodystrophy is likely involved in the development of the movement problems and other neurological abnormalities that occur in FAHN. Iron accumulation in the brain is probably also involved, although it is unclear how FA2H gene mutations lead to the buildup of iron.
People with FA2H gene mutations and some of the movement problems seen in FAHN were once classified as having a separate disorder called spastic paraplegia 35. People with mutations in this gene resulting in intellectual decline and optic nerve atrophy were said to have a disorder called FA2H-related leukodystrophy. However, these conditions are now generally considered to be forms of FAHN.
Read more about the FA2H gene.
How do people inherit fatty acid hydroxylase-associated neurodegeneration?
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Where can I find information about diagnosis or management of fatty acid hydroxylase-associated neurodegeneration?
These resources address the diagnosis or management of fatty acid hydroxylase-associated neurodegeneration and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about fatty acid hydroxylase-associated neurodegeneration?
You may find the following resources about fatty acid hydroxylase-associated neurodegeneration helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for fatty acid hydroxylase-associated neurodegeneration?
What if I still have specific questions about fatty acid hydroxylase-associated neurodegeneration?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding fatty acid hydroxylase-associated neurodegeneration?
acids ; ataxia ; atom ; atrophy ; autosomal ; autosomal recessive ; cell ; class ; demyelination ; dysarthria ; dysphagia ; dystonia ; enzyme ; fatty acids ; gait ; gene ; imaging ; infection ; inherited ; involuntary ; iron ; kinase ; leukodystrophy ; magnetic resonance imaging ; nervous system ; neurological ; nystagmus ; optic nerve ; oxygen ; palsy ; paraparesis ; paraplegia ; perception ; pneumonia ; pyramidal tract ; recessive ; spasticity ; strabismus ; visual acuity ; white matter
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (7 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.