Variable clinical phenotypes of alpha-methylacyl-CoA racemase deficiency: Report of four cases and review of the literature

Alpha-methylacyl-CoA-racemase (AMACR) deficiency (MIM#604489) is a peroxisomal disorder resulting in the accumulation of pristanic acid, dihydroxycholestanoic acid (DHCA), and trihydroxycholestanoic acid (THCA), with variable clinical features and age of onset from infancy to late adulthood. The purpose of this report is to define clinical variations and follow-up data in AMACR deficiency emphasizing treatment with a review of cases reported in the literature. Here, four patients, from two families, diagnosed with AMACR deficiency and showing phenotypic heterogeneity are presented. A 10-month-old-female presented with coagulopathy, hepatic dysfunction, and elevated pristanic acid, DHCA, and THCA levels. Genetic testing confirmed a homozygous variant c.596G>A in the AMACR gene. Her brother who had macrovesicular hepatosteatosis and elevated pristanic acid levels was diagnosed with family screening. The third patient presented with rhabdomyolysis following a strenuous exercise without any other complaint. Homozygous novel c.1006G>A variant was found on the AMACR gene. His asymptomatic sister carrying the same variant also had elevated pristanic acid levels. They had normal neuropsychologic evaluation. Dietary treatment with low phytanic and pristanic acid content was recommended to the patients but all showed poor compliance. The sibling pairs were followed for periods of 11 and 7 years, respectively. AMACR deficiency is usually described as an adult-onset disorder with neuropsychological problems. The characterization of natural history and new clinical phenotypes may support earlier diagnosis and treatment.