Newborn screening by tandem mass spectrometry of the heel stick dried blood spot identifies elevated levels of octanoylcarnitine (C8 acylcarnitine), usually accompanied by decanoyl (C10), hexanoyl (C6) and decenoyl (C10:1) carnitine esters. Also C8/C2 and C8/C10 ratios have been found informative for MCAD. When symptomatic, laboratory examination of blood may reveal hypoglycemia, metabolic acidosis, mild lactic acidosis, hyperammonemia, elevated BUN, and high uric acid levels. Serum transaminases are usually elevated. The urine often shows inappropriately low or absent ketones due to impaired fatty acid oxidation. Low serum and urine carnitines are typically found in the untreated patient. Biochemical testing of blood and urine for carnitine, acylcarnitines, acylglycines, and organic acids is diagnostic for this disorder. A generalized dicarboxylic aciduria is noted, characterized by elevations of suberylglycine and hexanoylglycine. In fibroblasts, the activity of medium chain acyl-CoA dehydrogenase is severely deficient in affected individuals, while heterozygous carriers for the disease usually have intermediate levels of activity, but are otherwise clinically and metabolically unaffected.
Detection of mutations in the MCAD gene on chromosome 1 in affected individuals confirms the biochemical results and accurately detects asymptomatic carriers among other family members. A common 985A>G mutation is responsible for up to 85% of cases. DNA analysis of postmortem tissue is possible when plasma and urine samples are not available. Prenatal diagnosis is possible by enzyme assay of amniocyte cultures. DNA analysis in amniocytes or chorionic villi can also be helpful in the diagnosis of an affected fetus in at-risk pregnancies.