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The 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.
Treatment of MSUD consists of metabolic support with emphasis on avoiding protein catabolism, hyperaminoacidemia, and acidosis. The total amount of fluid should be from 120 to 150 mL/kg to provide a total caloric intake of 150 to 170 kcal/kg per day, with 35% as carbohydrates, 50% as fat, and 15% as protein. The total protein, or at least 2.5 g/kg per day, should be given by oral or gavage feeding of infant formula that is free of branched-chain amino acids (BCAA). If orogastric feeding is not possible, and since there is no BCAA-free intravenous formula, the total protein intake should be limited to 1 g/kg per day. Thiamine 10 mg/kg per day should be used. Hemodialysis or peritoneal dialysis are seldom necessary. Response to therapy is gauged by blood leucine levels. The prognosis of MSUD is guarded, although early intervention may lead to a better prognosis.

Dihydrolipoyl dehydrogenase deficiency
The metabolic profile of dihydrolipoyl dehydrogenase deficiency includes laboratory findings similar to MSUD (Figure 73.1 B).

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.

 

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HMC-CoA lyase deficiency multiple carboxylase deficiency glutaric acidemia type II isovaleric acidemia dihydrolipoyl dehydrogenase deficiency maple syrup urine disease Brismar, 1990  Wendel, 1990 Lyon, 1996 Instructions  Wendel, 1990 De Vivo, 1990 Pause pointer over each bar or letter. Figure must be centered.