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Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency
ACADM gene
MCAD is a disorder of fatty acid oxidation caused by mutations in the ACADM gene. Presenting symptoms, which typically occur in childhood, include hypoglycemia, vomiting, lethargy, seizures and sudden infant death syndrome. Complications include respiratory difficulties, hepatic dysfunction, neurologic deficits and coma. The disorder is characterized by high mortality, however, milder variants exist and adult onset can occur. Significant phenotypic heterogeneity may occur even within a family. Infants with MCAD deficiency are often identified initially through newborn screening programs. Newborn screening reveals the accumulation of octanoylcarnitine, which is characteristic of MCAD deficiency. Follow-up testing for MCAD deficiency is usually by analysis of plasma acylcarnities, with confirmation by molecular diagnosis. In clinically diagnosed patients, and those patients whose initial newborn screening was confirmed using follow-up testing of plasma acylcarnitine and/or urinary organic acid analysis, mutation analysis identified a sequence variant in over 95% of cases. The K304E missense mutation accounts for up to 85% of mutant ACADM alleles, based on newborn screening in the United States, while the T121I mutation accounts for 95% of mutant ACADM alleles, based on newborn screening in Saudi Arabia.
For full sequencing, mutation analysis of the ACADM gene is performed on genomic DNA from the submitted specimen using bi-directional sequence analysis of exons 1-12. Mutations in exon 11, including the common K329E mutation (aka K304E), account for up to 85% of mutant ACADM alleles. For this reason, sequencing of exon 11 can be ordered first, followed by exons 1-10 and 12 if two mutations are not identified in Tier 1. For individuals of Saudi-Arabian descent, mutation specific testing for the p.T121I mutation that has been identified in this population on 95% of mutant ACADM alleles is available as a separate test. If sequencing identifies a mutation on only one allele of the ACADM gene, and if clinically indicated, reflex deletion/duplication testing (ExonArrayDx) will be performed at no additional charge to evaluate for a deletion/duplication of one or more exons of this gene. Mutations found in the first person of a family to be tested are confirmed by repeat analysis using sequencing, restriction fragment analysis, or another appropriate method.
Information Sheet, including prices and CPT codes
Consent Document
Genetic Test Sample Submission Form (Test Requisition Form) including Payment Options
MCAD, MCADD, ACADM, HELLP, Reye syndrome, urine organic analysis, acylglycines, SIDS, enzyme, carnitine, Lys304Glu, octanoic acid, decanoic acid, hexanoic acid, hexanoylglycine, phenylpropionylglycine, suberylglycine, palmitic acid, ketones, aciduria, fasting, newborn screening, dicarboxylic acids, 985A->G, K329E
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