Aims To study the demographic, clinical and laboratory findings, diagnoses and outcome of children under 5 years who were admitted with acute liver failure (ALF; INR > 2.0 or INR > 1.5 and encephalopathy) seconday to an underlying inherited metabolic disease (IMD).

Methods A retrospective case note review of children who were admitted between January 2001 to 2012 to a tertiary paediatric liver unit with ALF and a multi-centre review of their long term outcome.

Results A total of 127 children were identified from the database. 36 children (28%; 17 boys; median presenting age 6 weeks, range 1 day-41 months) had an underlying IMD including galactosemia in 17, mitochondrial cytopathy in 7, ornithine transcarbamylase (OTC) deficiency in 4, tyrosinemia type 1 in 4, Niemann-Pick C (NPC) in 3 and congenital disorder of glycosylation type 1 in 1. The remaining aetiologies were: indeterminate in 40 (32%), infectious in 15 (12%), neonatal hemochromatosis in 11 (9%), hemophagocytic syndrome in 8 (6%), drug toxicity in 5 (4%) and other in 10 (8%). Of the 36 children with an IMD consanguinity was present in 16 (44%), developmental delay in 3 (8%), jaundice at presentation in 28 (78%), hepatomegaly in 27 (75%) and encephalopathy in 8 (22%). The median peak (range) INR 4.8 (1.8–15), aspartate transaminase 334umol/L (39–15791) and bilirubin 227umol/L (13–692). Liver biopsy was done in 9 children (25%), neuroimaging in 10 children (28%), bone marrow aspiration in 7 (19%) and muscle biopsy in 5 (14%). 29/36 children with an IMD survived (81%). 4 children with mitochondrial cytopathy (including 1 after transplantation during the postoperative period) and 3 with NPC died. 4 children (1 OTC deficiency; 3 mitochondrial cytopathy) underwent liver transplantation. Follow up data was available for 23 children (mean follow up period, 4 years 3 months) in whom 13 (57%) were identified as having evidence of developmental delay.

Conclusion IMD is a common cause of ALF in children. Indeterminate cases may include undiagnosed metabolic diseases. Survival of children with IMD-related ALF is good, however, long term developmental outcome is less favourable.