The AMACR gene provides instructions for making an enzyme called alpha-methylacyl-CoA racemase (AMACR). This 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.
Health Conditions Related to Genetic Changes
Alpha-methylacyl-CoA racemase deficiency
Alpha-methylacyl-CoA racemase (AMACR) deficiency is caused by mutations in the AMACR gene. This disorder leads to a variety of neurological problems that begin in adulthood, including gradual loss in intellectual functioning (cognitive decline), seizures, and weakness and loss of sensation in the limbs due to nerve damage (sensorimotor neuropathy). Most individuals with AMACR deficiency have an AMACR gene mutation that replaces a protein building block (amino acid) called serine with an amino acid called proline at position 52 in the enzyme sequence, written as Ser52Pro or S52P. This mutation 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.More About This Health Condition
AMACR gene mutations that result in a lack of functional AMACR enzyme have also been identified in infants with a life-threatening disorder called congenital bile acid synthesis defect type 4. Babies with this disorder have cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to an enlarged liver (hepatomegaly) and irreversible liver disease (cirrhosis) in the first few months of life.
Some researchers consider congenital bile acid synthesis defect type 4 and AMACR deficiency (see above) to be variations of the same disorder. Because most individuals with congenital bile acid synthesis defect type 4 do not survive infancy, it is unclear whether they would have later developed the neurological symptoms seen in adults with AMACR deficiency.
Other Names for This Gene
- 2-methylacyl-CoA racemase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on 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. 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. 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. Review. Citation on PubMed