Life-threatening Intracranial Hemorrhage as the Initial Presentation of Genetically Confirmed Progressive Familial Intrahepatic Cholestasis Type 7 (PFIC-7): A Rare Case Report

Introduction

Progressive Familial Intrahepatic Cholestasis type 7 (PFIC-7) is a rare autosomal recessive cholestatic liver disorder caused by pathogenic variants in the USP53 gene. It typically presents during infancy with cholestatic jaundice, pruritus, and low/normal gamma-glutamyl transferase (GGT) levels. Fat-soluble vitamin deficiency resulting from chronic cholestasis may lead to severe bleeding complications, although intracranial hemorrhage as the presenting manifestation is exceedingly rare. We report an infant with genetically confirmed PFIC-7 presenting with life-threatening intracranial hemorrhage.

Methods

A 6-month-old infant presented with progressive jaundice, pruritus, intermittent acholic stools, and spontaneous ecchymoses. During hospitalization, the child developed lethargy, and neuroimaging revealed acute right subdural and subarachnoid hemorrhage with subsequent posterior cerebral artery infarction. Laboratory evaluation demonstrated conjugated hyperbilirubinemia, low-GGT cholestasis, prolonged PT/INR and aPTT, and elevated PIVKA-II, with normalization following vitamin K administration. Liver biopsy showed cholestasis, giant cell transformation, fibrosis, and bile ductular proliferation. Whole-exome sequencing performed on a buccal swab identified a homozygous, likely pathogenic USP53 splice-site variant (c.570-1G>A), confirming PFIC-7.

Results

The child was managed conservatively for intracranial hemorrhage and received ursodeoxycholic acid, medium-chain triglyceride supplementation, and vitamins A, D, E, and K. Coagulopathy resolved after vitamin K replacement, supporting vitamin K deficiency secondary to cholestasis as the cause of bleeding. At one-year follow-up, the child demonstrated age-appropriate neurodevelopment, satisfactory weight gain, stable liver function, and no recurrent neurological events, although long-term liver transplantation remains a possibility.

Conclusion

PFIC-7 should be considered in infants with low-GGT cholestasis and unexplained bleeding. Early recognition, prompt correction of fat-soluble vitamin deficiencies, multidisciplinary management, and molecular diagnosis are essential to prevent catastrophic complications and optimize long-term outcomes.