Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHAD)

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD deficiency) and Mitochondrial Trifunctional protein deficiency (MTP deficiency) also known as Trifunctional Protein (TFP) deficiency are disorders due to different defects in the MTP. MTP is an enzyme complex at the inner mitochondrial membrane with three enzymatic activities, long-chain 3-hydroxyacyl-CoA dehydrogenase, 2-enoyl hydratase and 3-keto acyl-CoA thiolase activities. Both isolated LCHAD deficiency and MTP deficiency, which has deficiencies in all 3 enzyme activities, have overlapping clinical presentations. The variable presentation includes infantile hypoketotic hypoglycemia, vomiting, lethargy, hypotonia, and failure to thrive. Additional presentations are cardiomyopathy and cardiac conduction defects, severe liver disease, recurrent muscle cramps, seizures, coma or sudden death (SIDS). Peripheral neuromyopathy, and pigmentary retinopathy may develop at a later age. The high mortality rate for these disorders, estimated at 38%, is usually due to a Reye-like illness or fatal cardiomyopathy. Syndromes of maternal illness, HELLP (hypertension, elevated liver enzymes, low platelets) and AFLP (acute fatty liver of pregnancy) may occur in a pregnancy carrying a fetus with LCHAD/MTP deficiency.