Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency (MCADD) Clinical Presentation

Updated: Mar 31, 2021
  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Presentation

History

Because medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive trait, other affected members of a family pedigree are unlikely to be historically available to assist in diagnosis.

The naturally frequent feeding of a very young infant tends to offset the need for reliance on alternative fuel for fasting; however, as the infant begins to extend the interval between feedings, the need for fatty acid catabolism correspondingly increases. Historically, this need may correlate with increased preprandial irritability, lethargy, jitteriness, sweating, and, possibly, seizures, which are all symptomatic of hypoglycemia.

Exaggerated lethargy accompanied by vomiting and acidosis with previous viral illness, often requiring intravenous fluid replacement therapy, is common. Indeed, in unrecognized cases, routine intravenous glucose and electrolyte rehydration may further obscure the underlying condition. It would be prudent to evaluate any infant or child with a repetitive history of postinfectious decompensation for fatty acid oxidative disorders.

Although early development is usually normal, growth may be somewhat slow. Repeated episodes of metabolic decompensation may result in poor intellectual development. [15]

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Physical

Prior to acute clinical presentation, physical examination findings may be entirely normal or may be remarkable only for a growth rate below the reference range.

Upon acute presentation, the infant is likely to be tachypneic, somnolent, and have a mildly enlarged liver, which is due to fatty infiltration. Hepatomegaly is a cardinal feature of MCAD, as well as of other fatty acid oxidative disorders. [16]

Neurological examination is nonspecific, without localizing signs.

If the infant has experienced a hypoglycemic seizure, distinguishing a postictal state from coma due to cerebral edema is vital.

The adult presentation may be characterized by headaches and vomiting, probably relating to hyperammonemia and to the cerebral metabolic effects of accumulated octanoate.

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Causes

The gene has been mapped to locus 1p31; more than 80 allelic variations have been reported. [17] The most common mutation is 985A>G, which refers to a substitution of a guanine nucleotide for an adenine nucleotide at the 985th residue. A second mutation, 583G>A, is reportedly common in certain populations. One study reported that individuals homozygous for 985A>G or 583G>A mutations had the highest levels of octanoylcarnitine, even when asymptomatic, and had the most severe clinical manifestations. [18] This has not been confirmed to date.

Phenotype-genotype relationships have been sought, with little success. As an example, although the common 985A>G mutation is frequently responsible for infantile onset, the same mutation has been reported in a patient with adult onset.

Acute hepatic failure in a previously healthy gravid female who is homozygous for the 985A>G mutation has been reported, thus confirming the potential for later onset, as well as the severity of complications with this specific mutation. [19]

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