Positive Newborn Screen for MCAD -- Now What?

Stephanie L. Austin, MS, MA; Laura A. Stokowski, RN, MS


July 10, 2014

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Medscape &

Diagnosis of MCAD Deficiency

In the expanded newborn screening era, diagnosis of MCAD deficiency on clinical grounds alone is less common, although symptoms can occur in the early neonatal period before the results of newborn screening are known. The diagnosis of MCAD deficiency can be based solely on biochemical testing (plasma acylcarnitine profile and urine organic acids). Other tests used by some programs to support or confirm the diagnosis or determine appropriate therapy include plasma L-carnitine levels, urinary acylglycines, enzyme analysis, and mutation analysis.

Repeat newborn screen. Some state laboratories will recommend repeating the filter paper newborn screen as the initial step in confirming the diagnosis of MCAD deficiency. However, states may use slightly different algorithms, so this step may or may not be recommended in a particular state. The recommendation for repeating the newborn screen is typical in the case of a preterm infant or when the first newborn screen was obtained before the infant was 24 hours old.

Plasma acylcarnitine profile. A plasma acylcarnitine profile provides levels of the individual fatty acids as well as ratios of medium-chain fatty acids, such as the C8/C10 ratio. In the presence of secondary carnitine deficiency, levels of C6-C10 acylcarnitines might not be significantly elevated,[15] but the C8/C10 ratio remains elevated.

Plasma total and free L-carnitine level. Patients with MCAD deficiency may have relatively low plasma levels of carnitine and an increased ratio of the acyl fraction to free carnitine.

Urinary acylglycines and organic acids. Elevated urinary hexanoglycine, suberylglycine, and medium-chain dicarboxylic acid levels support the diagnosis of MCAD deficiency. Acylglycines are glycine conjugates of acyl-CoA species and are endogenous intermediates of amino acid and fatty acid metabolism. Although not specific for MCAD deficiency, urinary acylglycines can serve as biochemical markers of this metabolic disorder.[9]

Mutation analysis. Sequencing is performed for mutations in the ACAMD gene, which is responsible for MCAD deficiency. Genetic testing is useful to supplement the biochemical diagnosis and for carrier testing for other family members and for future family planning.

Enzyme analysis. Measurement of the level of MCAD enzyme activity can be done using leukocytes, cultured fibroblasts, or other tissues.[9] The correlation of genotype and residual enzyme activity is of clinical relevance because it permits a prediction of the expected risk for metabolic decompensation that is otherwise difficult to determine.[16]


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