ERRORS OF PROTEIN METABOLISM
The cornerstone of the diagnosis of most of the inborn errors of protein metabolism that occur in neonates is knowing the metabolic pathway of leucine and remembering the amino acids that become elevated after each metabolic block (Figure 71.1). If all the metabolites of the leucine pathway are within normal limits, six of the most common inborn errors of protein metabolism that produce coma in the neonatal period can be excluded. The errors of protein metabolism that involve the leucine pathway are: (1) maple syrup urine disease (MSUD), (2) dihydrolipoyl dehydrogenase deficiency, (3) isovaleric acidemia, (4) glutaric acidemia type II, (5) multiple carboxylase deficiency, and (6) hydroxymethylglutarate-CoA lyase. Glycine encephalopathy, propionic and methylmalonic acidemia, and sulfite oxidase deficiency can occur in the neonatal period but they do not involve the leucine pathway and cannot be excluded by evaluating leucine metabolism. They are excluded if cerebrospinal fluid amino acids, blood amino and organic acids, urine organic acids, and urine sulfite are normal.
Figure 71.1.— Leucine pathway showing different enzymatic blocks and the amino acids that increase as a result of the block. A: maple syrup urine disease; B: dihydrolipoyl dehydrogenase deficiency; C: isovaleric acidemia; D: glutaric acidemia type II; E: multiple carboxylase deficiency; F: hydroxymethylglutarate (HMG)-CoA lyase deficiency.