Inherited metabolic disorders presenting as acute liver failure in newborns and young children: King's College Hospital experience.

Abstract

Acute liver failure (ALF) in children is a rare condition that is often fatal without liver transplantation. The diagnostic work-up is complex, and the etiology is unidentified in up to half of patients, making decisions like therapeutic transplantation extremely difficult. We collected clinical, laboratory, and outcome data on all patients under 5 years of age who were admitted between January 2001 and December 2011 to King's College Hospital with ALF secondary to an inherited metabolic disease (IMD), a common cause of pediatric acute liver failure. Thirty-six of 127 children with ALF had a metabolic etiology: galactosemia (17); mitochondrial respiratory chain disorder (MRCD, 7); ornithine transcarbamylase (OTC) deficiency (4); tyrosinemia type 1 (4); Niemann-Pick disease type C (NPC, 3); and congenital disorder of glycosylation type 1b (1). Seven children died: MRCD (4) and NPC (3). Four children were transplanted: OTC deficiency (1) and MRCD (3). Fifteen of 25 children followed up showed evidence of developmental delay. IMD is the most common group of disorders in this age group; indeterminate cases may yet include undiagnosed metabolic disorders; the overall survival rate is good but largely depends on diagnosis, while developmental outcome of the surviving patients is less favorable. • Up to half of children with ALF may be undiagnosed. • IMD is a common cause of pediatric acute liver failure. What is New: • Initial diagnostic clues may be gathered from the child's age and laboratory parameters. • Survival of children with IMD-related ALF is good, but developmental outcome is less favorable. • In the future, novel sequencing methods will aid in the diagnosis of disorders in which therapeutic decisions depend upon.