Alpha-methylacyl-CoA racemase (AMACR) deficiency is a disorder that causes a variety of neurological problems that begin in adulthood and slowly get worse. People with AMACR deficiency may have a gradual loss in intellectual functioning (cognitive decline), seizures, and migraines. They may also have acute episodes of brain dysfunction (encephalopathy) similar to stroke, involving altered consciousness and areas of damage (lesions) in the brain. Other features of AMACR deficiency may include weakness and loss of sensation in the limbs due to nerve damage (sensorimotor neuropathy), muscle stiffness (spasticity), and difficulty coordinating movements (ataxia). Vision problems caused by deterioration of the light-sensitive layer at the back of the eye (the retina) can also occur in this disorder.

AMACR deficiency is a rare disorder. Its prevalence is unknown. At least 10 cases have been described in the medical literature.

AMACR deficiency is caused by mutations in the AMACR gene. This gene provides instructions for making an enzyme called alpha-methylacyl-CoA racemase (AMACR).

The AMACR enzyme is found in the energy-producing centers in cells (mitochondria) and in cell structures called peroxisomes. Peroxisomes contain a variety of enzymes that break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production (synthesis) of fats (lipids) used in digestion and in the nervous system. In peroxisomes, the AMACR enzyme plays a role in the breakdown of a fatty acid called pristanic acid, which comes from meat and dairy foods in the diet. In mitochondria, AMACR is thought to help further break down the molecules derived from pristanic acid.

Most individuals with AMACR deficiency have an AMACR gene mutation that results in a lack (deficiency) of functional enzyme. The enzyme deficiency leads to accumulation of pristanic acid in the blood. However, it is unclear how this accumulation is related to the specific signs and symptoms of AMACR deficiency.

Genetic Testing Information

• Genetic Testing Registry: Alpha-methylacyl-CoA racemase deficiency

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• ALPHA-METHYLACYL-CoA RACEMASE DEFICIENCY; AMACRD

Scientific Articles on PubMed

• PubMed

• Dick D, Horvath R, Chinnery PF. AMACR mutations cause late-onset autosomal recessive cerebellar ataxia. Neurology. 2011 May 17;76(20):1768-70. doi: 10.1212/WNL.0b013e31821a4484. No abstract available. Citation on PubMed or Free article on PubMed Central
• Ferdinandusse S, Denis S, Clayton PT, Graham A, Rees JE, Allen JT, McLean BN, Brown AY, Vreken P, Waterham HR, Wanders RJ. Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Nat Genet. 2000 Feb;24(2):188-91. doi: 10.1038/72861. Citation on PubMed
• Ferdinandusse S, Denis S, IJlst L, Dacremont G, Waterham HR, Wanders RJ. Subcellular localization and physiological role of alpha-methylacyl-CoA racemase. J Lipid Res. 2000 Nov;41(11):1890-6. Citation on PubMed
• Haugarvoll K, Johansson S, Tzoulis C, Haukanes BI, Bredrup C, Neckelmann G, Boman H, Knappskog PM, Bindoff LA. MRI characterisation of adult onset alpha-methylacyl-coA racemase deficiency diagnosed by exome sequencing. Orphanet J Rare Dis. 2013 Jan 3;8:1. doi: 10.1186/1750-1172-8-1. Citation on PubMed or Free article on PubMed Central
• Wierzbicki AS. Peroxisomal disorders affecting phytanic acid alpha-oxidation: a review. Biochem Soc Trans. 2007 Nov;35(Pt 5):881-6. doi: 10.1042/BST0350881. Citation on PubMed