Elective Liver Transplantation for the Treatment of Classical Maple Syrup Urine Disease

Abstract

An 8.5-year-old girl with classical maple syrup urine disease (MSUD) required liver transplantation for hypervitaminosis A and was effectively cured of MSUD over an 8-year clinical follow-up period. We developed a collaborative multidisciplinary effort to evaluate the effects of elective liver transplantation in 10 additional children (age range 1.9-20.5 years) with classical MSUD. Patients were transplanted with whole cadaveric livers under a protocol designed to optimize safe pre-and post-transplant management of MSUD. All patients are alive and well with normal allograft function after 106 months of follow-up in the index patient and a median follow-up period of 14 months (range 4-18 months) in the 10 remaining patients. Leucine, isoleucine and valine levels stabilized within 6 hours post-transplant and remained so on an unrestricted protein intake in all patients. Metabolic cure was documented as a sustained increase in weight-adjusted leucine tolerance, normalization of plasma concentration relationships among branched-chain and other essential and nonessential amino acids, and metabolic and clinical stability during protein loading and intercurrent illnesses. Costs and risks associated with surgery and immune suppression were similar to other pediatric liver transplant populations.

Biochemical correlates of neuropsychiatric illness in maple syrup urine disease

“…To the extent that liver transplant can stabilize BCAA homeostasis during the early phase of brain development, transplantation early in life will likely afford the most substantial long-term benefit (3).…”

“…After the neonatal period, careful dietary management limits episodic decompensations to a variable extent, improves amino acid nutrition, and greatly reduces morbidity and mortality (2). Liver transplantation has recently emerged as an effective means to eliminate metabolic volatility and the risk of cerebral edema (3).…”

Branched Chain Amino Acids and Maple Syrup Urine Disease

“…Strauss et al [ 55 ] reviewed ten cases of orthotopic liver transplantation in classical MSUD patients. All patients were alive after a median follow-up period of 14 months and plasma amino acid concentration ratios were less variable and remained appropriately regulated through periods of dietary fl uctuation, fasting and illness although alloisoleucine remained detectable at low levels in the plasma.…”

Treatment and management issues in ataxic diseases

“…Typical treatable examples are abetalipoproteinemia (Granot and Kohen, 2004;Clarke et al, 2006), adrenomyeloneuropathy (Moser, 2006), cerebrotendinous xanthomatosis (Clemen et al, 2005), familial vitamin E deficiency (Mariotti et al, 2004), maple syrup urine disease (Morton et al, 2002;Strauss et al, 2006), pyruvate dehydrogenase deficiency (Klepper et al, 2004;Kaufmann et al, 2006;Stacpoole et al, 2006;Berendzen et al, 2006), Refsum's disease (Wierzbicki et al, 2002;Ruther, 2005), and Wilson's disease (Das and Ray, 2006). These readily identifiable disorders have been well reviewed with respect to diagnosis (Gray et al, 2000) and treatment (Gomez, 2001).…”