Early allograft dysfunction in a pediatric liver allograft with an occult pathogenic mutation in the urea cycle

Liver transplantation risks transferring a genetic defect in metabolic pathways, including the urea cycle. We present a case of pediatric liver transplantation complicated by metabolic crisis and early allograft dysfunction (EAD) in a previously healthy unrelated deceased donor. Allograft function improved with supportive care, and retransplantation was avoided. Because hyperammonemia suggested an enzymatic defect in the allograft, genetic testing from donor-derived deoxyribonucleic acid revealed a heterozygous mutation in the ASL gene, which encodes the urea cycle enzyme argininosuccinate lyase. Homozygous ASL mutations precipitate metabolic crises during fasting or postoperative states, whereas heterozygous carriers retain sufficient enzyme activity and are asymptomatic. In the described case, postoperative ischemia/reperfusion injury created a metabolic demand that exceeded the enzymatic capacity of the allograft. To our knowledge, this is the first report of an acquired argininosuccinate lyase deficiency by liver transplantation and underscores the importance of considering occult metabolic variants in the allograft during EAD.

Automated summary

Liver transplantation can transfer genetic defects in metabolic pathways, and this case highlights the occurrence of metabolic crisis and early allograft dysfunction due to an acquired argininosuccinate lyase deficiency. The recipient's genetic testing revealed a heterozygous mutation in the ASL gene, which encodes the urea cycle enzyme. Postoperative ischemia/reperfusion injury increased metabolic demand beyond the enzymatic capacity of the allograft. This case emphasizes the importance of considering occult metabolic variants in the allograft during early allograft dysfunction.