title: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  • 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.
authors.affiliation: Pediatric Liver Unit, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, UK. rhegarty@doctors.org.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Hegarty
authors.affiliation: Pediatric Liver Unit, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, UK. nedim.hadzic@kcl.ac.uk.
authors.forename: Nedim
authors.initials: N
authors.lastname: Hadzic
authors.affiliation: Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK. p.gissen@ucl.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Gissen
authors.affiliation: Pediatric Liver Unit, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, UK. anil.dhawan@kcl.ac.uk.
authors.forename: Anil
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D002675:Child, Preschool; D005500:Follow-Up Studies; D006785:Hospitals, University / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D017114:Liver Failure, Acute / Q000453:epidemiology / Q000209:etiology*; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D006113:United Kingdom / Q000453:epidemiology
keywords: Acute liver failure; Inherited metabolic disease; Liver transplantation; Pediatric