Definition of MCAD deficiency

Reviewed on 3/29/2021

MCAD deficiency: Deficiency of an enzyme that makes it impossible to digest certain kinds of fat. MCAD stands for medium-chain acyl-CoA dehydrogenase. Children born with MCAD deficiency cannot metabolize (digest) medium-chain fats such as coconut oil. If undiagnosed, the disorder can lead to metabolic collapse, coma and even death. Babies who survive run the risk of severe brain damage. Treatment involves strict attention to what the baby eats. The child has to avoid medium-chain fats in the diet. It is a life-long disorder. The special formula translates into a permanent diet change. MCAD deficiency affects about 1 of every 15,000 babies born in the US.

The gene for MCAD is located on chromosome 1p31. Over 25 MCAD gene variants have been reported. One of these gene variants, the K304E MCAD mutation, accounts for the majority of MCAD mutations identified to date. MCAD is an autosomal recessive disorder. Therefore, individuals who are homozygous or compound heterozygous for an MCAD mutation may have abnormal protein product and subsequent inefficient enzymatic activity to metabolize medium-chain fatty acids.

MCAD-deficient patients are at risk for a combination of the following outcomes: hypoglycemia (Low blood sugar), vomiting, lethargy, encephalopathy (brain disease), respiratory arrest, hepatomegaly (enlarged liver), seizures, apnea, cardiac arrest, coma, and sudden death. Long-term outcomes may include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit hyperactivity disorder (ADHD).

A precipitating factor is needed for clinical symptoms to present. It is often in times of metabolic stress induced by fasting or infection, when the demands on fatty acid oxidation are particularly high, that an MCAD-deficient patient may present with symptoms. Factors that may contribute to presentation and/or increased severity of clinical outcomes include prolonged fasting, infections or recent immunization, age, and family history of Sudden Infant Death Syndrome (SIDS) or MCAD deficiency.

MCAD mutations can be identified through DNA-based tests using polymerase chain reaction (PCR) and therefore can be detected in newborns by DNA analysis from newborn blood spots. Mass screening for MCAD deficiency, however, is generally conducted with the detection of abnormal metabolites in urine or blood by tandem mass spectrometry . Typically, this technique is used as an initial screening modality followed by confirmation of MCAD deficiency with urine organic acid profile or DNA mutation analysis. Testing for MCAD deficiency can be done as one of the battery of newborn screening tests.


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