Neonatal-onset Progressive Familial Intrahepatic Cholestasis (PFIC): first molecular study in Tunisian patients
##plugins.themes.academic_pro.article.main##
Abstract
Progressive familial intrahepatic is a heterogeneous group of rare autosomal recessive liver disorders. Neonatal onset is characteristic of the PFIC 1 and PFIC 2, which result from mutations in genes respectivelyATP8B1 and ABCB11.
Four Tunisian patients, three of them with PFIC 2 and one with PFIC1, were described. They all had typical clinical and biological features. However, they all had newly reported mutations. The same mutation was found in the patients with PFIC2, which could facilitate the diagnosis in Tunisian patients suspected in the future. The patient diagnosed with PFIC1 had also a newly described mutation, with a probable phenotypic particularity that is congenital hypothyroidism.
Advances are being made to establish a molecular diagnosis in neonatal onset cholestasis. Indeed, next generation sequencing gene panels (NGSGP) potentially decrease the need for invasive procedures in these patients, enable early initiation of treatment and adequate genetic counseling.
Keywords:
progressive familial intrahepatic cholestasis type 1 and 2, neonatal, mutation, ATP8B1, ABCB11, next generation sequencing gene panels##plugins.themes.academic_pro.article.details##
References
- References: 1. Rafaella A. Morotti¹, Frederick J. Suchy², and Margret S. Magid¹. Progressive familial intrahepatic cholestasis (PFIC) type 1, 2, and 3: a review of the liver pathology findings. Semin Liver Dis. 2011;31(1):3-10. 2. Anne Davit-Spraul¹, Emmanuel Gonzales²´³, Christiane Baussan¹, and Emmanuel Jacquemin²´³. Progressive Familial Intrahepatic cholestasis.Orphanet J Rare Dis. 2009;4:1. 3. Laura N. Bull, Richard J. Thompson. Progressive Familial Intrahepatic Cholestasis. Clin Liver Dis. 2018;22(4):657-69. 4. Karpen SJ, Kamath BM, Alexander II, et al. Use of a comprehensive 66 gene panel to diagnosis the cause of cholestasis in > 700 individuals. Hepatology. 2017;66(1):655A. [AASLD abstract]. 5. Chen HL LH, Wu JF, Wu SH, Chen HL, et al. Panel-based next-generation sequencing for the diagnosis of cholestatic genetic liver diseases: clinical utility and challenges. J Pediatr. 2018;205:153-9. 6. Whitington PF, Whitington GL. Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis. Gastroenterology. 1998;95:130-6. 7. Huey-Ling Chen, Shang-Hsin Wu, Shu-Hao Hsu, et al. Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases. J Biomed Sci. 2018;25:75. 8. W S Lee, P F Chai, L M Looi. Progressive Familial Intrahepatic Cholestasis in Malaysian patients - a report of five cases. Med J Malaysia. 2009;64:216-9. 9. Pawlikowska L, Strautnieks S, Jankowska I, et al. Differences in presentation and progression between severe FIC1 and BSEP deficiencies. J Hepatol. 2010;53(1):170-8. 10. Stapelbroek JM, Peters TA, Van Beurden DH, et al. ATP8B1 is essential for maintaining normal hearing. Proc Natl Acad Sci U S A. 2009;106(24):9709-14. 11. Eva Sticova, Milan Jirsa, and Joanna Pawlowska. New insights in genetic cholestasis: from molecular to clinical implications. J Gastroenterol Hepatol. 2018; 2018:2313675. 12. Emmanuel Jacquemin. Progressive familial intrahepatic cholestasis. Clinics and Research in Hepatology and Gastroenterology. 2012;36:26-35. 13. Andrew Fretzayas, Maria Moustaki, Olga Liapi, Themistocles Karpathios. Gilbert syndrome. Eur J Pediatr. 2012;171:11-5. 14. Emily Copeland, Nisa Renault, Marc Renault, Sarah Dyack, et al. Novel splice-site mutation in ATP8B1 results in atypical progressive familial intrahepatic cholestasis type 1. Journal of Gastroenterology and Hepatology. 2013;28:560-4. 15. Jara P, Hierro L, Martinez-Fernandez P, Alvarez-Doforna R, et al. Recurrence of bile salt export pump deficiency after liver transplantation. N Engl J Med. 2009;361:1359-67. 16. Stindt J, Kluge S, Droge C, Keitel V, et al. Bile salt export pump-reactive antibodies from a polyclonal, multi-inhibitory response in antibody-induced bile salt export pump deficiency. Hepatology. 2016;63:524-37. 17. Amy G. Feldman and Ronald J. Sokol. Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics. Nature Reviews Gastroenterology and Hepatology. 2019;16:346-60. 18. Metzker M.L. Sequencing technologies - the next generation. Nat Rev Genetic. 2010;11:31-46. 19. Marco Sciveres, Francesco Cirillo, Emmanuel Jacquemin, Giuseppe Maggiore. Diagnostic protocol of neonatal and infantile cholestasis: can it be improved? J of Pediatr. 2020;216:247. 20. Herbst S M et al. Taking the next step forward diagnosing inherited infantile cholestatic disorders with next generation sequencing. Mol Cell Probes. 2015;29:291-8.