serum and urine amino acid profiles of MSUD are characterized by the
accumulation of the branched-chain ketoacids produced by the block in
the pathways of leucine (Figure 73.1 A), isoleucine, and valine (Figure
73.2 A), and the accumulation of alloisoleucine. Alloisoleucine is a
by-product of isoleucine that only occurs when there is an excess of
isoleucine. Alloisoleucine is found in all neonates with MSUD.
Figure 73.1.— 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.
The metabolic abnormality of dihydrolipoyl dehydrogenase also includes lactic acidosis due to pyruvate dehydrogenase and high concentration of alpha-ketoglutarate due to citric acid cycle dysfunction (Figure 73.2 B).
Figure 73.2.— 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.
Treatment of dihydrolipoyl dehydrogenase deficiency consists of metabolic support with emphasis on avoiding protein catabolism, hyperaminoacidemia, and acidosis. It is guided by the same principles as the treatment of MSUD. The prognosis of dihydrolipoyl dehydrogenase deficiency is poor.