S5571 Progressive Familial Intrahepatic Cholestasis Type 3: A Rare Cause of Chronic Liver Disease in a Young Woman

Introduction: Progressive familial intrahepatic cholestasis (PFIC), refers to a group of inherited autosomal recessive disorders that cause rapidly progressive intrahepatic cholestasis. PFIC is classified into 3 types: PFIC1, PFIC2, PFIC3. PFIC3 is the rarest, with an incidence of 1 in 5,00,000 births, it is caused by mutations in the ATP binding cassette subfamily B member 4 gene (ABCB 4) located on chromosome 7, that encodes multidrug resistance class III (MDR3) protein crucial for bile secretion. Case Description/Methods: A 15 year-old female patient, presented with complaints of insidious onset and gradually progressing pedal edema, abdominal distension, facial puffiness. She reported history of similar complaints 4 months prior. Clinical examination revealed moderate splenomegaly. Ultrasonography demonstrated coarsely echo textured liver with surface irregularities and moderate splenomegaly measuring 11 cm. Laboratory investigations demonstrated Hb 8.9 g/dl, Platelet count of 1,70,000/μL, Serum bilurubin 2.9 mg/dL, SGOT 202 U/L, SGPT 96 U/L, alkaline phosphatase 310 U/L, gamma-glutamyl transferase 107 U/L, SAAG of 1.5. T3: 0.63 ng/ml, TSH: 7.49 ml U/L. Twenty-four hour urinary copper: 62 mg/day, Serum Ceruloplasmin: 25 mg/dl, magnetic resonance imaging brain shows symmetrical T1 hyperintesities in bilateral basal ganglia. UGI endoscopy shows G-2 Esophageal varices. Liver biopsy shows altered architecture with mild rosetting, mild lobular inflammation. Portal tracts show infiltration by lymphoplasmacytic cells and polymorphs. Portal fibrosis present, copper staining seen. Genetic analysis revealed mutation of ABCB4 on chr7. Discussion: PFIC 3 is a rare autosomal recessive disease defined by mutations in the ABCB4 gene, which encodes the MDR3 protein. Dysfunction of MDR3 due to ABCB4 mutations cause impaired PtdCho secretion, leading to the accumulation of unneutralized bile salts, causing bile salt-induced injury to the biliary epithelium and bile canaliculi thus acquiring cholestasis, advanced liver disease and cirrhosis. Clinically PFIC 3 manifests within first year of life with symptoms of cholestasis that may progress to cirrhosis and end-stage liver damage over time. Older children typically have symptoms of portal hypertension such as splenomegaly and hematemesis. Given its rarity and overlapping clinical features with other hepatobiliary diseases, diagnosis is heavily reliant on genetic testing thereby causing significant delays. Its low prevalence and variable presentation, poses PFIC3 as a diagnostic challenge, underscoring the importance of understanding this medical rarity.