Differential Intraoperative Effect of Liver Transplant in Different Inborn Errors of Metabolism.

Liver transplant (LT) is a therapeutic option for a growing number of inborn errors of metabolism (IEM), including some disorders not confined to the liver. Clinical advantages of LT in maple syrup urine disease (MSUD), methylmalonic acidemia (MMA), and argininosuccinic aciduria (ASA) have been reported. However, no information on the early metabolic effect of LT after portal reperfusion is available in these disorders. Here we describe the intraoperative differential metabolic outcome of LT in MSUD, MMA, and ASA. In these IEM, LT promptly cleared toxic metabolites to safe concentrations. In MSUD, leucine concentration reached physiological concentration within 12 hours after portal reperfusion. In MMA and ASA, LT allowed faster clearance of methylmalonate and argininosuccinate, respectively, both dropping by ∼90% within the first hour after portal reperfusion. The early biochemical benefits of LT in MSUD, MMA, and ASA demonstrate its immediate effectiveness in protecting patients from intercurrent metabolic decompensations.

Differential response to renal replacement therapy in neonatal-onset inborn errors of metabolism.

Severe urea cycle defects (UCD), organic acidemias (OA) and maple syrup urine disease (MSUD) are life-threatening disorders presenting in the first days of life. Renal replacement therapy (RRT) is an emergency option in affected newborns, mostly performed as ultima ratio. We report our 10-year experience using emergency RRT in newborns with UCD, OA and MSUD. Twelve newborns (eight with UCD, two with methylmalonic acidemia and two with MSUD) underwent emergency RRT. The overall survival rate to RRT was 58.3%. Hyperammonemic newborns required earlier RRT with respect to MSUD patients (75 (65-102) vs 301 (192-410) h of life, P < 0.01). Hyperammonemic neonates surviving (n = 5) and non-surviving (n = 5) the acute neonatal decompensation showed similar birth weight (P = 0.690), duration of intubation (P = 0.917), ammonia at onset (P = 0.916) and at the start of RRT (P = 0.426), age at RRT (P = 0.999) and duration of coma before RRT (P = 0.691). Remarkably, all survivors quickly responded to RRT, with ammonia concentration less than 300 µmol/L after 8 h of treatment. One patient with UCD successfully treated by neonatal RRT died at 4 months of life because of sepsis. All patients with MSUD had normalized leucine levels after 12 h of RRT, surviving the acute neonatal decompenstation. All long-term survivors (five liver transplanted, one waiting for liver transplantation) currently show normal or near-normal neurological development (48 ± 39 months of age). Early response to RRT was associated with survival irrespective of pre-treatment picture. RRT can be considered even in huge neonatal metabolic decompensations. Early liver transplantation may be an option for select patients.