Maple syrup urine disease: Treatment of the acutely ill newborn

Abstract

Three patients with maple syrup urine disease were treated during the acute neonatal stage. Multiple exchange transfusions proved to be a satisfactory means of achieving rapid clinical and biochemical improvement during this phase. On the other hand, evidence is provided suggesting that in addition to exchange transfusions, a high calorie intake above 150 Cal/kg body weight/day is necessary to lower the plasma concentration of the branched chain amino acids to near-normal levels. As long as this calorie intake was not provided, further exchange transfusions failed to lower the plasma leucine concentration to below 17 mg/100 ml in one patient. It is assumed that this high calorie intake is necessary to prevent the breakdown of endogenous protein. Treatment of acute episodes in maple syrup urine disease should therefore not only eliminate the elevated alpha-keto acids and branched chain amino acids quickly (i.e. by multiple exchange transfusions or peritoneal dialysis), but in addition should provide a high calorie intake.

Peritoneal dialysis in maple-syrup-urine disease: Studies on branched-chain amino and keto acids

“…The initial course of our patient C.R has been reported by Hammersen et al [10]. Dietary management in this child during the first 18 months of life was very difficult.…”

“…Moreover, in the newborn period at the time of initial diagnosis extremely elevated concentrations of BCAA's and BCKA's have been observed in the blood and cerebrospinal fluid. In these situations the low renal elimination of the "neuro-toxic" metabolites [16] can necessitate multiple exchange transfusions [10,23] …”

Maple syrup urine disease-therapeutic use of insulin in catabolic states

“…This catabolic mechanism is enhanced during deficient nutrition and diarrhea [1]. There is evidence that negative nitrogen balance is also present during exchange transfusion [10,16,21]. If in patients with MSUD the release of branched-chain amino acids occurs they are unable to further degrade the branched-chain keto acids.…”

“…Previously the provision of additional calories in MSUD patients during catabolic states has been recomended [10,18], but, this measure does not necessarily induce anabolism. Clow and coworkers [6] have proposed the use of intravenous lipid (2-4 g/kg/day) during the acute phase in order to bypass a theoretically existing block in pyruvate oxidation by high branchedchain keto acid concentrations.…”

“…Neurological symptoms arise when a-ketoisocaproate and leucine blood levels exceed 1 mM. Extremely high blood and tissue levels of branched-chain amino and keto acids require urgent treatment by peritoneal dialysis or exchange transfusion [6,10,20,21].…”