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 300mol/L after 8h of treatment. One patient with UCD successfully treated by neonatal RRT died at 4months of life because of sepsis. All patients with MSUD had normalized leucine levels after 12h 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 +/- 39months 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.