Maddirevula et al. (2019) reported 3 patients in a large consanguineous Saudi family (family 5) with infantile-onset cholestasis. The patients presented in infancy with jaundice, elevated AST and ALT, elevated alkaline phosphatase (ALP), normal GGT, and persistent hypocalcemia. All had intractable itching. One patient underwent successful liver transplant at age 6 years; she was alive at 23 years old with normal liver function tests and no itching. Her sister presented at age 5 months with hypocalcemic seizures and high ALP; she was alive at age 15 years with her native liver and normal ALT/AST levels. A 3-year-old male cousin was similarly affected. The itching in the latter 2 patients was responsive to rifampicin. The sisters developed deafness at 14 and 9 years of age, respectively. The younger male cousin did not have deafness.

Zhang et al. (2020) reported 7 unrelated Chinese patients with PFIC7 who presented with jaundice by 7 months of age. The patients were treated successfully with medications, and all were confirmed to be alive with their native livers at age 5 years, except 1 who was lost to follow-up. Serum total bilirubin normalized by 2 years of age, and transaminases returned to normal in half of the patients. Liver biopsies showed lobular disarray, hepatocellular and canalicular cholestasis, giant cell changes, fibrosis, and cirrhosis. Immunostaining for USP53 was unsuccessful, but the interacting proteins TJP2 (607709) and CLDN1 (603718) were decreased and blurred on liver biopsies. Ultrastructural studies showed elongated tight junction complexes. One patient had hearing problems from birth, whereas another developed transient hearing problems in the first months of life. None of the other patients had hearing problems.

Bull et al. (2021) reported 4 unrelated patients (patients 4-7) with PFIC7 confirmed by genetic analysis. The onset of the disorder varied between infancy and 15 years. Features included jaundice, pruritis, and diarrhea. Most patients had recurrent attacks of cholestasis associated with normal GGT, variably elevated ALT and AST, and hyperbilirubinemia. All were alive between 10 and 21 years of age without undergoing liver transplant. The spleen was enlarged in 2 patients. Liver biopsy showed canalicular and hepatocellular cholestasis and portoseptal or bridging fibrosis. USP53 immunostaining was unsuccessful. There were no abnormalities of epithelial tight junction morphology on electron microscopic analysis, although there were some structural abnormalities of the desmosome. Bull et al. (2021) noted that the only patient (patient 6) with a missense variant (P242L) presented at 15 years of age, the latest of the patient cohort. Audiometry was not performed in these patients, although none reported hearing problems.