alpha-methylacyl-CoA racemase deficiency

Alpha-methylacyl-CoA racemase deficiency is an inherited metabolic disorder that chiefly affects the nervous system and eyes. It results from harmful changes in the AMACR gene, which encodes an enzyme needed to break down certain branched-chain fatty acids and bile acids. Symptoms usually begin in adolescence or adulthood, although liver problems can appear in infancy. Precise prevalence figures are not available, but published reports suggest the condition is very uncommon worldwide. Severity and symptoms vary widely between individuals, even among siblings with the same genetic change.

Most people first seek medical attention for neurological problems. Cognitive decline, focal-onset seizures, tremor, migraine, spasticity, and progressive weakness on one side of the body (hemiparesis) are frequently reported. Over time, many individuals develop sensorimotor neuropathy that affects balance and coordination as well as hyperreflexia and intention tremor. Visual difficulties are another hallmark: constriction of the peripheral visual field, rod–cone dystrophy, cataracts, and pigmentary changes in the retina can lead to significant visual impairment. Depression and other mood changes may accompany the neurological course. Not all individuals experience all features, and the pace at which symptoms appear can differ considerably.

The disorder is caused by pathogenic variants in the AMACR gene. The AMACR enzyme converts (racemizes) certain branched-chain fatty acids and bile acid intermediates into a form that can be further broken down for energy. When the enzyme is missing or has greatly reduced activity, these substrates accumulate and damage nerve cells, the retina, and occasionally the liver. Alpha-methylacyl-CoA racemase deficiency follows an autosomal recessive inheritance pattern: an individual must receive one altered AMACR gene from each parent to be affected. Parents who each carry one altered copy are usually healthy but have a 25% chance with every pregnancy of having an affected child. The condition may be more common when parents share a common ancestor because they are more likely to carry the same rare variant. Genetic counseling is recommended for families who have an affected child or who know they are carriers.

Currently, management focuses on supportive care and symptom management. Seizures are treated with standard anti-seizure medications, while physical and occupational therapy address weakness, tremor, and spasticity. Low-vision services help people adapt to progressive visual loss, and mental health support is important for those experiencing depression. Because this condition can affect multiple organ systems, coordinated multidisciplinary care is recommended, typically involving neurologists, ophthalmologists, rehabilitation specialists, and genetic counselors. Regular surveillance is an essential part of long-term care, including periodic neurological examinations, ophthalmologic evaluations, and monitoring of metabolic markers to detect emerging complications early. Patients should discuss individualized management plans with their healthcare team.

The long-term outlook depends on which symptoms develop first, how rapidly they progress, and how early supportive interventions begin. Some individuals maintain independence for many years, while others experience increasing neurological disability that impacts mobility and vision. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with inherited metabolic and neuro-ophthalmologic disorders to plan ongoing care and to adjust support as needs change.

Clinical trials are underway exploring new treatment approaches, reflecting growing research interest in this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.