Question

In fatty acid metabolism, one of the metabolic order defects is MCAD (medium-chain acyl-
CoA dehydrogenase) deficiency, an autosomal recessive disorder, where vomiting and
lethargy are triggered when an affected individual does not eat for an extended period of
time. A different, rarer, disorder is MCAT (medium-chain ketoacyl-CoA thiolase) deficiency,
which presents in similarly to MCAD, though has rarely been reported.

Why do you think these two disorders are rare, and what would the difference in metabolites be (i.e. which
disorder builds up which molecules?

Answer 1

MCAD (medium-chain acyl-CoA dehydrogenase) deficiency as given in the question is an autosomal recessive disorder. Which means that the patient will have two copies of the non-working (mutated) gene for this particular disease which they got from both the parents. The parents are not affected and are only carriers. The condition arises only when there are two copies of the gene and that is why this is a rare condition (1 out of every 15,000 babies inj the U.S.A). This condition leads to a situation where the body is unable to breakdown certain fats. The affected people are unable to change some of the fats they eat into energy needed by the body to function. An enzyme called medium-chain acyl-CoA dehydrogenase is needed for breaking down medium-length fatty acids. This enzyme is in deficient numbers or nonworking in the affected individuals. This leads to accumulation of unused medium-length fatty acids which can even cause brain damage and respiratory problems. Properly treated at the earlier stage the patients life can be saved.

The second disorder MCAT (medium-chain ketoacyl-CoA thiolase) deficiency is also a similar disease. But the genetic base of the disorder has not been completely understood. The medium-chain ketoacyl-CoA thiolase enzyme is responsible for breaking down certain medium length fatty acids. In medium-chain ketoacyl-CoA thiolase deficiency (MCAT) this enzyme is in deficient numbers or nonworking in the affected individuals.