Liver transplantation for non-hepatotoxic inborn errors of metabolism

Abstract

Hepatic-based inborn errors of metabolism are targets for treatment with liver transplantation in children, in whom the metabolic defect causes irreversible damage to the liver. However, certain metabolic defects originate with enzyme deficiencies localized in the liver but then give rise to toxic intermediates that damage extrahepatic organs without any significant compromise of general liver function. Here, the rationale of using liver transplantation to replace an organ that is functioning normally except for a specific metabolic pathway raises difficult questions about indications for transplantation, timing, amount of replacement tissue needed to correct the defect, and whether heterozygote parents are suitable living donors for liver transplantation in their affected children. This review explores these questions and others, including the role of hepatocyte transplantation, in this select group of disorders. Until the promise of specific gene or enzyme replacement therapy is realized, liver and hepatocyte transplantation offers the best chance of achieving metabolic control in these challenging patients.

Long-term outcome following pediatric liver transplantation for metabolic disorders

“…In some cases, a metabolic crisis may strike at any time, leading to mortality or neurological impairment in survivors. Therefore, liver transplantation has been an increasingly important therapeutic option for many inborn errors of metabolism (1). Successful liver transplantation has been reported for a variety of metabolic conditions, including α 1 ‐antitrypsin deficiency (2, 3), urea cycle disorders (4), tyrosinemia type 1 (5), MSUD (6), organic acidemias (7, 8), glycogen storage disorders (9), primary hyperoxaluria type 1 (10, 11), Wilson disease (12), and mitochondrial respiratory chain disorders (13).…”

Curative Treatment of Ornithine Transcarbamylase Deficiency With a Liver Transplant: A Case Report

“…6 The liver is the main source of urea cycle enzymes. If patients with OTC deficiency do not respond to medical and conservative therapy, liver transplant is a good alternative for patients with the missing enzyme.…”

Living donor liver transplantation for pediatric patients with metabolic disorders: The Japanese multicenter registry

“…Metabolic decompensation can result in severe neurological sequelae and even mortality in some patients with inborn errors of metabolism . LT has become an important therapeutic modality and may offer a complete/partial cure for many metabolic disorders . Metabolic disorders have become the second largest indication for LT .…”