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.
Conclusion: 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.
What is Known: • 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. |
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Abbreviations
- ACAD9:
-
Acyl-CoA dehydrogenase 9 deficiency
- ALF:
-
Acute liver failure
- AST:
-
Aspartate aminotransferase
- CDG:
-
Congenital disorder of glycosylation
- DD:
-
Developmental delay
- FAOD:
-
Fatty acid oxidation defect
- HE:
-
Hepatic encephalopathy
- IMD:
-
Inherited metabolic disease
- INR:
-
International normalized ratio
- MRCD:
-
Mitochondrial respiratory chain disorder
- NPC:
-
Niemann-Pick disease type C
- OLT:
-
Orthotopic liver transplantation
- OTC:
-
Ornithine transcarbamylase
- PT:
-
Prothrombin time
- WBC:
-
White blood cell
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Acknowledgments
We thank Ashish Dhawan, an honorary research assistant, for his help in collecting data.
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The authors declare that they have no conflict of interest.
Authors’ contributions
AD came up with the idea of the article. RH collected the data and drafted the manuscript. NH, PG, and AD were involved in critically revising it. All authors approved the final version of the manuscript for publication.
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Hegarty, R., Hadzic, N., Gissen, P. et al. Inherited metabolic disorders presenting as acute liver failure in newborns and young children: King’s College Hospital experience. Eur J Pediatr 174, 1387–1392 (2015). https://doi.org/10.1007/s00431-015-2540-6
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DOI: https://doi.org/10.1007/s00431-015-2540-6