PHENOTYPIC AND GENOTYPIC CHARACTERISTICS OF PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS TYPE 3 IN PEDIATRIC POPULATION IN PAKISTAN

OBJECTIVE: To determine the phenotypic and genotypic characteristics of progressive familial intrahepatic cholestasis (PFIC) type 3 in Pakistani children in a hospital setting. METHODS: This cross-sectional observational study was conducted at department of Pediatrics Gastroenterology & Hepatology, The Children’s Hospital Lahore, Pakistan from October 2020 to March 2021. Patients of either sex under 16 years of age presenting with jaundice, pruritus, neonatal cholestasis or with chronic liver and gamma glutamyl transferase >100 IU/ml were included in the study after taking informed consent by parents. For Molecular genetics 2ml blood in EDTA was sent to an international laboratory free of cost on research basis. Reports were assessed and levels were noted and genetic coding was also recorded. Data was entered and analyzed in SPSS version 22. Molecular data was interpreted with the help of clinical geneticist. RESULTS: Out of 34 children, 14 (41.2%) were males and 20 (58.8%) were females. Mean age of children was 6.71±3.10 years. Consanguinity was noted in 32 (94.1%) parents having positive family history in 24 (70.6%) cases. The most common mutation was c. 1783C>T p.(Arg595*),  noted in 12 (35.3%) cases, followed by c. 2861G>T p.(Gly954 ASP) [8 (23.5%) cases], c. 153G>A p.(Trp51) [3 (8.8%) cases], c. 1714 C>T p.(Gln572*) c. 1906C>T p. (Gln636), c. 3220G>A p.(Gly1074Arg, c. 3433del p. (val1145Leufsx7)  in 2 (5.9%) cases each, c. 3859 C>T p.(1287Argext*) c. 88-91del p.(Lys30gly fsx7) and c. 1429c>T p. (Gln477) in one (2.9%) case each. CONCLUSION: Children with PFIC type 3 have variable phenotypic and genotypic presentation.