A case report of progressive familial intrahepatic cholestasis in neonatal practice

Progressive familial intrahepatic cholestasis is a group of infrequent hereditary diseases caused by the defect in the transport of bile acids, leading to the rapid development of the liver’s cirrhosis. The infrequent occurrence of this pathology creates significant difficulties in the diagnostic search for the causes of intrahepatic cholestasis. The article demonstrates a clinical case of progressive familial intrahepatic cholestasis in a newborn child. We used the descriptive method of clinical-anamnestic and laboratory-instrumental data, obtained from the medical history of a full-term newborn who was treated in the perinatal center of the Regional Clinical Hospital (Omsk). Starting from the first days of life, signs of liver failure with a progressive increase drew: indirect hyperbilirubinemia followed by predominance of direct bilirubin, hemorrhagic syndrome with signs of disturbance of both external and internal hemostasis pathways, and hypoproteinemia. At the second stage of nursing, monitoring was carried out laboratory and instrumental studies and using results we excluded the surgical and infectious nature of the pathology: hepatitis B and C, cytomegalovirus infection. In a diagnostic searching we were looking for the most common genetically determined liver diseases. Using massive parallel sequencing for mutations in 47 genes which have the hereditary nature of liver damage, we excluded tyrosinemia, galactosemia, Gaucher’s disease, and alpha-1-antitrypsin deficiency. According to the results of a liver biopsy performed at the clinic of the federal center of the St Petersburg State Pediatric Medical University detected progressive familial intrahepatic cholestasis (Byler’s disease). This case belongs to the category of orphan diseases with a complex diagnostic search, has a familial nature of inheritance (patient’s brother dead due to certain hereditary liver’s disease) and requires molecular genetic confirmation.

1. Ipatova MG, Ponkratenko LV, Chubarova AI, Shumilov PV, Sergienko EYu. A complex case of progressive familial intrahepatic cholestasis type 2 diagnostics. Pediatriya – Zhurnal im G.N. Speranskogo. 2017;96(6): 76–80. (In Russ.) https://doi.org/10.24110/0031-403X-2017-96-6-76-80.

2. Mukhina YuG, Degtyareva AV. Neonatal cholestasis syndrome. Part 1. Doktor. Ru. 2010;(1):22–27. (In Russ.) Available at: https://www.elibrary.ru/mpwcfx.

3. Hassan S, Hertel P. Overview of Progressive Familial Intrahepatic Cholestasis. Clin Liver Dis. 2022;26(3):371–390. https://doi.org/10.1016/j.cld.2022.03.003.

4. Srivastava A. Progressive familial intrahepatic cholestasis. J Clin Exp Hepatol. 2014;4(1):25–36. https://doi.org/10.1016/j.jceh.2013.10.005.

5. Amirneni S, Haep N, Gad MA, Soto-Gutierrez A, Squires JE, Florentino RM. Molecular overview of progressive familial intrahepatic cholestasis. World J Gastroenterol. 2020;26(47):7470–7484. https://doi.org/10.3748/wjg.v26.i47.7470.

6. Baker A, Kerkar N, Todorova L, Kamath BM, Houwen RHJ. Systematic review of progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2019;43(1):20–36. https://doi.org/10.1016/j.clinre.2018.07.010.

7. Vinayagamoorthy V, Srivastava A, Sarma MS. Newer variants of progressive familial intrahepatic cholestasis. World J Hepatol. 2021;13(12):2024–2038. https://doi.org/10.4254/wjh.v13.i12.2024.

8. Felzen A, Verkade HJ. The spectrum of Progressive Familial Intrahepatic Cholestasis diseases: Update on pathophysiology and emerging treatments. Eur J Med Genet. 2021;64(11):104317. https://doi.org/10.1016/j.ejmg.2021.104317.

9. Alam S, Lal BB. Recent updates on progressive familial intrahepatic cholestasis types 1, 2 and 3: Outcome and therapeutic strategies. World J Hepatol. 2022;14(1):98–118. https://doi.org/10.4254/wjh.v14.i1.98.

10. Succoio M, Sacchettini R, Rossi A, Parenti G, Ruoppolo M. Galactosemia: Biochemistry, Molecular Genetics, Newborn Screening, and Treatment. Biomolecules. 2022;12(7):968. https://doi.org/10.3390/biom12070968.

11. Wheeler S, Sillence DJ. Niemann-Pick type C disease: cellular pathology and pharmacotherapy. J Neurochem. 2020;153(6):674–692. https://doi.org/10.1111/jnc.14895.

12. Kohut TJ, Gilbert MA, Loomes KM. Alagille Syndrome: A Focused Review on Clinical Features, Genetics, and Treatment. Semin Liver Dis. 2021;41(4):525–537. https://doi.org/10.1055/s-0041-1730951.

13. Dev S, Kruse RL, Hamilton JP, Lutsenko S. Wilson Disease: Update on Pathophysiology and Treatment. Front Cell Dev Biol. 2022;10:871877. https://doi.org/10.3389/fcell.2022.871877.

14. Tang Y, Kong Y. Hereditary tyrosinemia type l: newborn screening, diagnosis and treatment. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021;50(4):514–523. (In Chinese) https://doi.org/10.3724/zdxbyxb-2021-0255.

15. Carubbi F, Cappellini MD, Fargion S, Fracanzani AL, Nascimbeni F. Liver involvement in Gaucher disease: A practical review for the hepatologist and the gastroenterologist. Dig Liver Dis. 2020;52(4):368–373. https://doi.org/10.1016/j.dld.2020.01.004.

16. Suri A, Patel D, Teckman JH. Alpha-1 Antitrypsin Deficiency Liver Disease. Clin Liver Dis. 2022;26(3):391–402. https://doi.org/10.1016/j.cld.2022.03.004.

17. Semenova N, Kamenets E, Annenkova E, Marakhonov A, Gusarova E, Demina N et al. Clinical Characterization of Alagille Syndrome in Patients with Cholestatic Liver Disease. Int J Mol Sci. 2023;24(14):11758. https://doi.org/10.3390/ijms241411758.

18. Karadag N, Zenciroglu A, Eminoglu FT, Dilli D, Karagol BS, Kundak A et al. Literature review and outcome of classic galactosemia diagnosed in the neonatal period. Clin Lab. 2013;59(9-10):1139–1146. https://doi.org/10.7754/clin.lab.2013.121235.

19. Patterson MC, Clayton P, Gissen P, Anheim M, Bauer P, Bonnot O et al. Recommendations for the detection and diagnosis of Niemann-Pick disease type C: An update. Neurol Clin Pract. 2017;7(6):499–511. https://doi.org/10.1212/CPJ.0000000000000399.

20. Chanpong A, Dhawan A. Wilson disease in children and young adults – State of the art. Saudi J Gastroenterol. 2022;28(1):21–31. https://doi.org/10.4103/sjg.sjg_501_21.