Fatty Acid Hydroxylase-associated Neurodegeneration, is caused by a mutation in the FA2H gene. FAHN is a rare NBIA disorder. Onset usually occurs in childhood featuring leg dystonia, muscle spasticity, weakness, falling, optic nerve atrophy and later the affected individuals develop progressive intellectual impairment,  seizures, profound cerebellar atrophy and white matter changes in the brain, in addition to high brain iron.

At present, only a few families have been identified with this rare form of NBIA. However two other neurologic conditions, leukodystrophy and hereditary spastic paraplegia 35 (HSP35), were previously thought of as separate disorders, but are now included in the spectrum of FAHN.


T2-weighted MRI views of the brain with findings showing hypointensity of the globus pallidus and possibly variable unilateral or bilateral symmetric white matter hyperintensity. Bone marrow biopsy, although not necessary for diagnosis, may demonstrate accumulation of granular histiocytes.

The diagnosis of FAHN may be suspected in individuals with the onset of hallmark features in the first or second-decade: spasticity, ataxia, dystonia, optic atrophy, eye movement abnormalities early in the disease course and progressive intellectual impairment and seizures later in the disease course. Spastic paraplegia or quadriplegia and pyramidal tract signs, dysarthria (difficulty pronouncing words), and dysphagia (difficulty swallowing) are other features.

Note: Fewer than 30 individuals with FAHN have been reported; the phenotype is likely to expand as more cases are ascertained, and thus the designation of any phenotypic feature as ‘hallmark’ may be premature.

Diagnosis of FAHN is confirmed through genetic testing of the FA2H gene to find two gene changes. At least one FA2H gene change is found through DNA sequence analysis in >95% of individuals.

If no gene change or only one gene change is found through sequence analysis of the FA2H gene, then genetic testing may proceed to deletion/duplication analysis.

Rarely, an individual with the signs and symptoms of FAHN will have only one or even no FA2H gene changes identified. This can happen because the genetic testing is not perfect and has certain limitations. It does not mean the person does not have FAHN; it may just mean we do not yet have the technology to find the hidden gene change. In these cases it becomes very important to have doctors experienced with FAHN review the MRI and the person’s symptoms very carefully to be as sure as possible of the diagnosis.


Symptoms of FAHN are mostly confined to the central nervous system (the brain and spine) and usually start to appear during childhood or the teenage years.

Common symptoms

Corticospinal tract involvement (communication pathway between brain and limbs)

Movement disorder(s)

Eye exams

MRI findings for FAHN

A T2 sequence is the preferred type of MRI for FAHN diagnosis because it is highly sensitive to the detection of brain iron which is important clue to confirm it.

FAHN Evaluation

The extent of disease in an individual diagnosed with FAHN can be evaluated by


There is no standard treatment for FAHN. A team of medical professionals recommends treatments based on current symptoms.

Therapies to manage dystonia

Long-term management


FAHN is a progressive disease, but the declines in health occur at irregular intervals. Between declines, there can be periods of relative clinical stability (when the patient’s symptoms do not get worse). However, skills that an individual has lost are usually not regained. As the disease progresses, dystonia and spasticity make it harder for the person to walk and eventually lead to wheelchair use.

Premature death may occur in the 20s or 30s due to a combination of nutrition-related immunodeficiency and respiratory compromise. However, the average life span is variable.


A change in the FA2H gene impairs the function of fatty acid 2-hydroxylase whose role is normally to modify the fatty acids. The altered function of FA2H results into a abnormal myelin which is composed of fatty acids. Myelin is the protective layer which insulates nerves and helps with the rapid transmission of nerve signals. A change in the FA2H gene results in weak myelin that is prone to deterioration and leads to the development of the movement problems and other neurological abnormalities seen in FAHN. FA2H is the only gene known to cause FAHN.

The FA2H gene that is altered in those with FAHN is inherited in an autosomal recessive manner.“Autosomal” refers to the fact that the FA2H gene is located on chromosome 16,which is one of the autosomes (chromosome pairs 1-22). “Recessive” refers to the fact that a gene change must be present in both copies of the FA2H gene for a person to have FAHN. If an individual has only one FA2H gene change, then they are called a “carrier” for FAHN. Carriers do not have health problems related to that gene change and often do not know they carry a recessive gene change.

If two carriers have a child then there is a 25% chance that they will both pass on their recessive FA2H gene changes and have a child with FAHN.There is a 50% chance that the child will be a carrier like his/her parents and a 25% chance that the child will not have FAHN or be a carrier.

Carrier testing for at-risk relatives and prenatal testing for pregnancies at risk are suggested if both disease-causing mutations have been identified in an affected family member.

Prenatal Testing

If the disease-causing mutations have been identified in the family, prenatal diagnosis for pregnancies at increased risk can be done. In one test, DNA is extracted from fetal cells obtained by amniocentesis, usually at 15 to 18 weeks’ gestation, and analyzed. Or, sampling is done of the chorionic villus, the tiny finger-like projections on the edge of the placenta, usually at 10 to 12 weeks’ gestation.

Embryo screening, known as preimplantation genetic diagnosis, may be an option for some families in which the disease-causing mutations have been identified.


Please see the link for more detailed clinical information on FAHN at Gene Reviews, which was used as a source for some of the above information. Gene Reviews is primarily for the use of genetics professionals so the terminology and information may be difficult to understand for the general public.

For other medical information please see www.nbiacure.org

Gene Reviews Authors: Michael C Kruer, MD, Allison Gregory, MS CGC, and Susan J Hayflick, MD.