ERRORS OF PROTEIN METABOLISM THAT INVOLVE THE LEUCINE PATHWAY
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 deficiency.
Branched chain beta-keto acid dehydrogenase deficiency
A block in the metabolism of leucine due to branched chain beta-keto acid dehydrogenase deficiency occurs in MSUD and in dihydrolipoyl dehydrogenase deficiency (Figure 72.1 A, B).
Figure 72.1.— 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: HMG-CoA lyase deficiency.
syrup urine disease
Figure 72.2.— Metabolic pathways involved in branched chain amino acid disorders. A: maple syrup urine disease; B: dihydrolipoyl dehydrogenase deficiency; C: isovaleric acidemia; D: glutaric acidemia type II; E: multiple carboxylase deficiency; F: HMG-CoA lyase deficiency.
Three findings may suggest MSUD prior to the serum amino acid result: (1) a burnt sugar smell in the urine; (2) an interictal EEG with runs of 5 to 7 Hz monophasic, central, or parasagittal negative activity during awake or sleep; or (3) a brain imaging study showing dorsal brainstem edema (Figure 72.3).