Pediatric Gastroenterology, Hepatology & Nutrition

The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (대한소아소화기영양학회)
권호 표지
DOI QR코드

DOI QR Code

Presentation of Progressive Familial Intrahepatic Cholestasis Type 3 Mimicking Wilson Disease: Molecular Genetic Diagnosis and Response to Treatment

  • Boga, Salih (Division of Digestive Diseases and Section of Transplantation and Immunology, Department of Medicine and Surgery, Yale University School of Medicine) ;
  • Jain, Dhanpat (Department of Pathology, Yale University School of Medicine) ;
  • Schilsky, Michael L. (Division of Digestive Diseases and Section of Transplantation and Immunology, Department of Medicine and Surgery, Yale University School of Medicine)
  • Received : 2015.04.18
  • Accepted : 2015.05.28
  • Published : 2015.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disorder of cholestasis of hepatocellular origin, typically seen in infancy or childhood caused by a defect in the ABCB4 located on chromosome 7. Here we report on an older patient, aged 15, who presented with biochemical testing that led to an initial consideration of a diagnosis of Wilson disease (WD) resulting in a delayed diagnosis of PFIC3. Diagnosis of PFIC3 was later confirmed by molecular studies that identified novel mutations in the ABCB4 gene. Cholestasis due to PFIC3 can cause elevated hepatic copper and increased urine copper excretion that overlap with current diagnostic criteria for WD. Molecular diagnostics are very useful for establishing the diagnosis of PFIC3. Ursodeoxycholic acid ameliorates cholestasis in PFIC3, and may help mediate a reduction in hepatic copper content in response to treatment.

Keywords

References

  1. Jacquemin E. Progressive familial intrahepatic cholestasis. Genetic basis and treatment. Clin Liver Dis 2000;4:753-63. https://doi.org/10.1016/S1089-3261(05)70139-2
  2. Jacquemin E. Role of multidrug resistance 3 deficiency in pediatric and adult liver disease: one gene for three diseases. Semin Liver Dis 2001;21:551-62. https://doi.org/10.1055/s-2001-19033
  3. Baussan C, Cresteil D, Gonzales E, Raynaud N, Dumont M, Bernard O, et al. Genetic cholestatic liver diseases: the example of progressive familial intrahepatic cholestasis and related disorders. Acta Gastroenterol Belg 2004;67:179-83.
  4. Shneider BL. ABCB4 disease presenting with cirrhosis and copper overload-potential confusion with Wilson disease. J Clin Exp Hepatol 2011;1:115-7. https://doi.org/10.1016/S0973-6883(11)60131-X
  5. Ramraj R, Finegold MJ, Karpen SJ. Progressive familial intrahepatic cholestasis type 3: overlapping presentation with Wilson disease. Clin Pediatr (Phila) 2012;51:689-91. https://doi.org/10.1177/0009922812451076
  6. European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol 2012; 56:671-85. https://doi.org/10.1016/j.jhep.2011.11.007
  7. Sternlieb I, Quintana N. Biliary proteins and ductular ultrastructure. Hepatology 1985;5:139-43. https://doi.org/10.1002/hep.1840050127
  8. Wendum D, Barbu V, Rosmorduc O, Arrive L, Flejou JF, Poupon R. Aspects of liver pathology in adult patients with MDR3/ABCB4 gene mutations. Virchows Arch 2012;460:291-8. https://doi.org/10.1007/s00428-012-1202-6
  9. Sannier A, Ganne N, Tepper M, Ziol M. MDR3 immunostaining on frozen liver biopsy samples is not a sensitive diagnostic tool for the detection of heterozygous MDR3/ABCB4 gene mutations. Virchows Arch 2012;460:535-7. https://doi.org/10.1007/s00428-012-1231-1
  10. Jacquemin E, Hermans D, Myara A, Habes D, Debray D, Hadchouel M, et al. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology 1997;25:519-23. https://doi.org/10.1002/hep.510250303
  11. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis 2009;4:1. https://doi.org/10.1186/1750-1172-4-1
  12. Lai J, Taouli B, Iyer KR, Arnon R, Thung SN, Magid MS, et al. Cholangiolocellular carcinoma in a pediatric patient with small duct sclerosing cholangitis: a case report. Semin Liver Dis 2012;32:360-6.
  13. Jacquemin E, De Vree JM, Cresteil D, Sokal EM, Sturm E, Dumont M, et al. The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood. Gastroenterology 2001;120:1448-58. https://doi.org/10.1053/gast.2001.23984

Cited by

  1. Leberbiopsie bei Kindern und Jugendlichen : Initiale morphologische Untersuchungen bei diffusen Lebererkrankungen vol.38, pp.4, 2015, https://doi.org/10.1007/s00292-017-0306-9
  2. New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications vol.2018, pp.None, 2015, https://doi.org/10.1155/2018/2313675
  3. Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset vol.2, pp.5, 2015, https://doi.org/10.1002/hep4.1149
  4. Update on the Diagnosis and Management of Wilson Disease vol.20, pp.12, 2018, https://doi.org/10.1007/s11894-018-0660-7
  5. ABCB4 disease mimicking morbus Wilson: A potential diagnostic pitfall vol.164, pp.1, 2015, https://doi.org/10.5507/bp.2019.054
  6. Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice? vol.2, pp.4, 2015, https://doi.org/10.1016/j.jhepr.2020.100114
  7. Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation vol.21, pp.1, 2015, https://doi.org/10.1186/s12881-020-01173-0
  8. Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease vol.9, pp.9, 2015, https://doi.org/10.3390/biomedicines9091100