In beta-oxidation cycle disorders, there are numerous inherited defects, which typically manifest during fasting with hypoglycemia and metabolic acidosis; some cause cardiomyopathy and muscle weakness.
Beta-oxidation cycle disorders (see the table) are among the fatty acid and glycerol metabolism disorders.
See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism and testing for suspected inherited disorders of metabolism.
Acetyl CoA is generated from fatty acids through repeated beta-oxidation cycles. Sets of 4 enzymes (an acyl dehydrogenase, a hydratase, a hydroxyacyl dehydrogenase, and a lyase) specific for different chain lengths (very long chain, long chain, medium chain, and short chain) are required to catabolize fatty acids completely.
Inheritance for all fatty acid oxidation defects is autosomal recessive.
Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
This deficiency is the most common defect in the beta-oxidation cycle.
Clinical manifestations typically begin after 2 to 3 months of age and usually follow fasting (as little as 12 hours). Patients have vomiting and lethargy that may progress rapidly to seizures, coma, and sometimes death (which can also appear as sudden unexpected infant death). During attacks, patients have hypoglycemia, hyperammonemia, and unexpectedly low urinary and serum ketones. Metabolic acidosis is often present but may be a late manifestation.
neonatal screening in all states in the United States.
Maintenance requirements); some clinicians also advocate carnitine supplementation during acute episodes.
Prevention is a low-fat, high-carbohydrate diet and avoidance of prolonged fasting. Cornstarch therapy is often used to provide a margin of safety during overnight fasting.
Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD)
This deficiency is the second most common fatty acid oxidation defect. It shares many features of MCADD, but patients may also have cardiomyopathy; rhabdomyolysis, massive creatine kinase elevations, and myoglobinuria with muscle exertion; peripheral neuropathy; and abnormal liver function. A mother whose fetus has LCHADD often has HELLP syndrome (hemolysis, elevated liver function tests, and low platelet count) during pregnancy.
neonatal screening in all states in the United States.
Treatment during acute exacerbations includes hydration, high-dose glucose, bed rest, urine alkalinization, and carnitine supplementation. Long-term treatment includes a high-carbohydrate diet, medium-chain triglyceride supplementation, and avoidance of fasting and strenuous exercise.
Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD)
This deficiency is similar to LCHADD but is commonly associated with significant cardiomyopathy.
Glutaric Acidemia Type II
A defect in the transfer of electrons from the coenzyme of fatty acyl dehydrogenases to the electronic transport chain affects reactions involving fatty acids of all chain lengths (multiple acyl-coA dehydrogenase deficiency); oxidation of several amino acids is also affected.
Clinical manifestations thus include fasting hypoglycemia, severe metabolic acidosis, and hyperammonemia.
Diagnosis of glutaric acidemia type II is by increased ethylmalonic, glutaric, 2- and 3-hydroxyglutaric, and other dicarboxylic acids in organic acid analysis, and glutaryl and isovaleryl and other acylcarnitines in tandem mass spectrometry studies. DNA analysis can be confirmatory.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man (OMIM) database: Complete gene, molecular, and chromosomal location information
