European Journal of Pediatrics

, Volume 174, Issue 10, pp 1387–1392 | Cite as

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

  • Robert Hegarty
  • Nedim Hadzic
  • Paul Gissen
  • Anil Dhawan
Original Article
First Online:
Received:
Revised:
Accepted:

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.

Keywords

Acute liver failure Pediatric Inherited metabolic disease Liver transplantation 

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

This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

We thank Ashish Dhawan, an honorary research assistant, for his help in collecting data.

Conflict of interest

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.

References

  1. 1.
    Bariş Z, Saltik Temızel IN, Uslu N, Usta Y, Demır H, Gürakan F, Ozen H, Yüce A (2012) Acute liver failure in children: 20-year experience. Turk J Gastroenterol 23:127–134PubMedGoogle Scholar
  2. 2.
    Bhaduri BR, Mieli-Vergani G (1996) Fulminant hepatic failure: pediatric aspects. Semin Liver Dis 16:349–355CrossRefPubMedGoogle Scholar
  3. 3.
    Campeau PM, Pivalizza PJ, Miller G, McBride K, Karpen S, Goss J, Lee BH (2010) Early orthotopic liver transplantation in urea cycle defects: follow up of a developmental outcome study. Mol Genet Metab 1:S84–S87CrossRefGoogle Scholar
  4. 4.
    Dhawan A, Cheesman P, Mieli-Vergani G (2004) Approaches to acute liver failure in children. Pediatr Transplant 8:584–588CrossRefPubMedGoogle Scholar
  5. 5.
    Dhawan A, Mieli-Vergani G (2005) Acute liver failure in neonates. Early Hum Dev 81:1005–1010CrossRefPubMedGoogle Scholar
  6. 6.
    Durand P, Debray D, Mandel R, Baujard C, Branchereau S, Gauthier F, Jacquemin E, Devictor D (2001) Acute liver failure in infancy: a 14-year experience of a pediatric liver transplantation center. J Pediatr 139:871–876CrossRefPubMedGoogle Scholar
  7. 7.
    He M, Rutledge SL, Kelly DR, Palmer CA, Murdoch G, Majumder N, Nicholls RD, Pei Z, Watkins PA, Vockley J (2007) A new genetic disorder in mitochondrial fatty acid beta-oxidation: ACAD9 deficiency. Am J Hum Genet 81:87–103PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Jumbo-Lucioni P et al (2012) Diversity of approaches to classic galactosemia around the world: a comparison of diagnosis, intervention, and outcomes. J Inherit Metab Dis 35:1037–1049PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    McKiernan PJ, Ball S, Santra S, Gupte G, Sharif K, Hickman K, McFarland R, Fratter C, Poulton J, Rahman S, Taylor RW (2013) Incidence of mitochondrial disease in children presenting with acute liver failure under 2 years of age. J Pediatr Gastroenterol Nutr 56S2:62Google Scholar
  10. 10.
    Narkewicz MR, Dell Olio D, Karpen SJ, Murray KF, Schwarz K, Yazigi N, Zhang S, Belle SH, Squires RH (2009) Pattern of diagnostic evaluation for the causes of pediatric acute liver failure: an opportunity for quality improvement. J Pediatr 155:801–806PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    National Health Service Blood and Transplant (2013) Liver transplantation; selection criteria and recipient registration. [PDF] Available via http://www.odt.nhs.uk/pdf/liver_selection_policy.pdf [Accessed 12 September 2014]
  12. 12.
    Psacharopoulos HT, Mowat AP, Davies M, Portmann B, Silk DB, Williams R (1980) Fulminant hepatic failure in childhood: an analysis of 31 cases. Arch Dis Child 55:252–258PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Rüegger CM, Lindner M, Ballhausen D et al (2014) Cross-sectional observational study of 208 patients with non-classical urea cycle disorders. J Inherit Metab Dis 37:21–30PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Schweitzer-Krantz S (2003) Early diagnosis of inherited metabolic disorders towards improving outcome: the controversial issue of galactosemia. Eur J Pediatr 162:S50–S53CrossRefPubMedGoogle Scholar
  15. 15.
    Shanmugam NP, Bansal S, Dhawan A (2012) Acute liver failure in children and adolescents. In: Dhawan A (ed) Concise pediatric and adolescent hepatology. Karger, Basel, Chapter 2Google Scholar
  16. 16.
    Squires RH Jr (2008) Acute liver failure in children. Semin Liver Dis 28:153–166CrossRefPubMedGoogle Scholar
  17. 17.
    Squires RH Jr, Shneider BL, Bucuvalas J et al (2006) Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 148:652–658PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Sundaram SS, Alonso EM, Narkewicz MR, Zhang S, Squires RH, Pediatric Acute Liver Failure Study Group (2011) Characterization and outcomes of young infants with acute liver failure. J Pediatr 159:813–818PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Robert Hegarty
    • 1
  • Nedim Hadzic
    • 1
  • Paul Gissen
    • 2
  • Anil Dhawan
    • 1
  1. 1.Pediatric Liver UnitKing’s College Hospital NHS Foundation TrustLondonUK
  2. 2.Metabolic Medicine UnitGreat Ormond Street Hospital for Children NHS Foundation TrustLondonUK

Personalised recommendations