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Metabolic Liver Disease: When to Suspect and How to Diagnose?

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Abstract

Metabolic liver diseases are still considered by many as a ‘rare’ diagnosis, though scenario has definitely changed in recent times. With recent advances and wider availablility of newer techniques, many of these are now amenable to diagnosis and optimum management. Though the logistics involved are still out of reach of a significant proportion of our population, a stepwise and methodological approach with simple diagnostic tests can help point towards a probable diagnosis (with resultant directed investigations), helping to avoid unnecessary and costly workup. This review focuses on diagnostic protocol-based approach to common metabolic liver diseases encountered frequently in pediatric hepatology.

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References

  1. PALF study group. Acute liver failure in children: the first 348 patients in Pediatric Acute Liver Failure Study Group. J Pediatr. 2006;148:652–8.

  2. Lee WS, Mckiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom. J Pediatr Gastroenterol Nutr. 2005;40:575–81.

    Article  PubMed  Google Scholar 

  3. Dhawan A Etiology and prognosis of acute liver failure in children. Liver Transpl. 2008;14:S80–4.

    Article  PubMed  Google Scholar 

  4. Arora NK, Arora S, Ahuja A, et al. Alpha 1 antitrypsin deficiency in children with chronic liver disease in North India. Indian Pediatr. 2010;47:1015–23.

    Article  PubMed  Google Scholar 

  5. Yachha SK, Sharma BC, Khanduri A, Srivastava A. Current spectrum of hepatobiliary disorders in Northern India. Indian Pediatr. 1997;34:885–90.

    CAS  PubMed  Google Scholar 

  6. Poddar U, Thapa BR, Das A, Bhattacharya A, Rao KL, Singh K. Neonatal cholestasis: differentiation of biliary atresia from neonatal hepatitis in a developing country. Acta Paediatr. 2009;98:1260–4.

    Article  PubMed  Google Scholar 

  7. Koshy A, Ramaswamy K, Correa M, Rekha S. Glycogen storage disease: report of 17 cases from Southern India. Indian J Gastroenterol. 2006;25:182–4.

    PubMed  Google Scholar 

  8. Alam S, Lal BB, Khanna R, Sood V, Rawat D. Acute liver failure in infants and young children in a specialized pediatric liver centre in India. Indian J Pediatr. 2015;82:879–83.

    Article  PubMed  Google Scholar 

  9. Janssen MC, de Kleine RH, van den Berg AP, et al. Successful liver transplantation and long-term follow-up in a patient with MPI-CDG. Pediatrics. 2014;134:e279–83.

    Article  PubMed  Google Scholar 

  10. Morava E. Galactose supplementation in phosphoglucomutase-1 deficiency; review and outlook for a novel treatable CDG. Mol Genet Metab. 2014;112:275–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Léticée N, Bessières-Grattagliano B, Dupré T, et al. Should PMM2-deficiency (CDG Ia) be searched in every case of unexplained hydrops fetalis? Mol Genet Metab. 2010;101:253–7.

    Article  CAS  PubMed  Google Scholar 

  12. Whybra C, Mengel E, Russo A, et al. Lysosomal storage disorder in non-immunological hydrops fetalis (NIHF): more common than assumed? Report of four Cases with Transient NIHF and a Review of the Literature. Orphanet J Rare Dis. 2012;7:86.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Boles RG, Buck EA, Blitzer MG, et al. Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life. J Pediatr. 1998;132:924–33.

    Article  CAS  PubMed  Google Scholar 

  14. Karall D, Brunner-Krainz M, Kogelnig K, et al. Clinical outcome, biochemical and therapeutic follow-up in 14 Austrian patients with long-chain 3-hydroxy acyl CoA dehydrogenase deficiency (LCHADD). Orphanet J Rare Dis. 2015;10:21.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sugita G, Tsuyoshi H, Nishijima K, Yoshida Y. Fructose-1,6-bisphosphatase deficiency: a case of a successful pregnancy by closely monitoring metabolic control. JIMD Rep. 2014;14:115–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rajanayagam J, Coman D, Cartwright D, Lewindon PJ. Pediatric acute liver failure: etiology, outcomes, and the role of serial pediatric end-stage liver disease scores. Pediatr Transplant. 2013;17:362–8.

    Article  CAS  PubMed  Google Scholar 

  17. Kaur S, Kumar P, Kumar V, Sarin SK, Kumar A. Etiology and prognostic factors of acute liver failure in children. Indian Pediatr. 2013;50:677–9.

    Article  PubMed  Google Scholar 

  18. Sundaram SS, Alonso E, Narkewicz MR, Zhang S, Squires RH; Pediatric Acute Liver Failure Study Group. Characterization and outcome of young infants with acute liver failure. J Pediatr. 2011;159:813–8.e1.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Durand P, Debray D, Mandel R, et al. Acute liver failure in infancy: a 14-year experience of a pediatric liver transplantation center. J Pediatr. 2001;139:871–6.

    Article  CAS  PubMed  Google Scholar 

  20. Brett A, Pinto C, Carvalho L, Garcia P, Diogo L, Gonçalves I. Acute liver failure in under two year-olds–are there markers of metabolic disease on admission? Ann Hepatol. 2013;12:791–6.

    PubMed  Google Scholar 

  21. Mazariegos G, Shneider B, Burton B, et al. Liver transplantation for pediatric metabolic diseases. Mol Genet Metab. 2014;111:418–27.

    Article  CAS  PubMed  Google Scholar 

  22. Amon R, Kerkar N, Davis MK, Anand R, Yin W, González-Peralta RP; SPLIT Research Group. Liver transplantation in children with metabolic diseases: the studies of pediatric liver transplantation experience. Pediatr Transplant. 2010;14:796–805.

    Article  Google Scholar 

  23. Stevenson T, Millan MT, Wayman K, et al. Long-term outcome following pediatric liver transplantation for metabolic disorders. Pediatr Transplant. 2010;14:268–7.

    Article  PubMed  Google Scholar 

  24. Gallagher RC, Lam C, Wong D, Cederbaum S, Sokol RJ. Significant hepatic involvement in patients with ornithine transcarbamylase deficiency. J Pediatr. 2014;164:720–5.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Subramaniam P, Clayton PT, Portmann BC, Mieli-Vergani G, Hadzić N. Variable clinical spectrum of the most common inborn error of bile acid metabolism–3beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency. J Pediatr Gastroenterol Nutr. 2010;50:61–6.

    Article  CAS  PubMed  Google Scholar 

  26. Molho-Pessach V, Rios JJ, Xing C, Setchell KD, Cohen JC, Hobbs HH. Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology. Hepatology. 2012;55:1139–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Porto AF. Lysosomal acid lipase deficiency: diagnosis and treatment of Wolman and Cholesteryl ester storage diseases. Pediatr Endocrinol Rev. 2014;12:125–32.

    PubMed  Google Scholar 

  28. Zhang B, Porto AF. Cholesteryl ester storage disease: protean presentations of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr. 2013;56:682–5.

    Article  CAS  PubMed  Google Scholar 

  29. Bernstein DL, Hülkova H, Bialer MG, Desnick RJ. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013;58:1230–43.

    Article  CAS  PubMed  Google Scholar 

  30. Khanna R, Alam S, Sherwani R, Arora S, Arora NK, Malik A. Alpha-1 antitrypsin deficiency among Indian children with liver disorders. Indian J Gastroenterol. 2006;25:191–3.

    PubMed  Google Scholar 

  31. Zhang ZH, Lin WX, Deng M, et al. Clinical, molecular and functional investigation on an infant with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). PLoS One. 2014;9:e89267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rathi N, Rathi A. Galactosemia presenting as recurrent sepsis. J Trop Pediatr. 2011;57:487–9.

    Article  PubMed  Google Scholar 

  33. Ananth N, Praveenkumar GS, Rao KA. Vasanthi, kakkilaya S. Two cases of hereditary fructose intolerance. Indian J Clin Biochem. 2003;18:87–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sørensen M, Mikkelsen KS, Frisch K, Villadsen GE, Keiding S. Regional metabolic liver function measured in patients with cirrhosis by 2-[18F]fluoro-2-deoxy-D-galactose PET/CT. J Hepatol. 2013;58:1119–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Akar M, Celik M, Kasapkara CS, Ozbek MN, Aldudak B, Tuzun H. Mutational analysis of the galactose-1-phosphate uridyltransferase (GALT) gene in southeast part of Turkey: a regional report. Genet Couns. 2015;26:91–4.

    CAS  PubMed  Google Scholar 

  36. Koliofoti EG, Gkentzi D, Varvarigou A, Trigka M, Schulpis K. Rare case of homozygous epimerase deficiency and heterozygous of duarte 2 variant. J Pediatr Endocrinol Metab. 2014;27:947–9.

    Article  PubMed  Google Scholar 

  37. European Association for Study of Liver. EASL clinical practice guidelines: Wilson’s disease. J Hepatol. 2012;56:671–85.

    Article  Google Scholar 

  38. Morris AA, Taanman JW, Blake J, et al. Liver failure associated with mitochondrial DNA depletion. J Hepatol. 1998;28:556–63.

    Article  CAS  PubMed  Google Scholar 

  39. Goldenthal MJ, Kuruvilla T, Damle S, et al. Non-invasive evaluation of buccal respiratory chain enzyme dysfunction in mitochondrial disease: comparison with studies in muscle biopsy. Mol Genet Metab. 2012;105:457–62.

    Article  CAS  PubMed  Google Scholar 

  40. Burdelski M, Rodeck B, Latta A, et al. Treatment of inherited metabolic disorders by liver transplantation. J Inherit Metab Dis. 1991;14:604–18.

    Article  CAS  PubMed  Google Scholar 

  41. Hughes RD, Mitry RR, Dhawan A. Current status of hepatocyte transplantation. Transplantation. 2012;93:342–7.

    Article  CAS  PubMed  Google Scholar 

  42. Cantz T, Sharma AD, Ott M. Concise review: cell therapies for hereditary metabolic liver diseases-concepts, clinical results, and future developments. Stem Cells. 2015;33:1055–62.

    Article  CAS  PubMed  Google Scholar 

  43. Piccolo P, Brunetti-Pierri N. Gene therapy for inherited diseases of liver metabolism. Hum Gene Ther. 2015;26:186–92.

    Article  CAS  PubMed  Google Scholar 

  44. Nicholson SA, Moyo B, Arbuthnot PB. Progress and prospects of engineered sequence-specific DNA modulating technologies for the management of liver diseases. World J Hepatol. 2015;7:859–73.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Seema Alam.

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SA conceptualized and designed the work. SA and VS acquired, analysed, reviewed the data and prepared first draft. SA critically reviewed, revised, approved the final version and will act as guarantor for the paper.

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Alam, S., Sood, V. Metabolic Liver Disease: When to Suspect and How to Diagnose?. Indian J Pediatr 83, 1321–1333 (2016). https://doi.org/10.1007/s12098-016-2097-z

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  • DOI: https://doi.org/10.1007/s12098-016-2097-z

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