Alpha-methylacyl-CoA racemase deficiency /AMACR deficiency
Incidence
AMACR deficiency is a rare disorder. Its prevalence is unknown. At least 10 cases have been described in the medical literature. Prevalence: <1 / 1 000 000. Update 2017/ MGJM.
Clinical Characteristics
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. Alpha-methylacyl-CoA racemase is a mitochondrial and peroxisomal enzyme that catalyzes the conversion of 2R stereoisomers of phytanic and pristanic acid to their S counterparts. AMACR is essential for beta oxidation of branched-chain fatty acids and bile acid intermediates, such as dihydroxycholestanoic acid and trihydroxycholestanoic acid. 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. Cytogenetic location: 5p13.2 .
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
Diagnosis is based on liquid secondary ionization mass spectrometry (LSIMS), gas chromatography-mass spectrometry (GC-MS) and electrospray ionization-tandem mass spectrometry analysis of urine, serum and bile. Serum pristanic acid and C27 bile acid intermediates are increased.