cholestasis, progressive familial intrahepatic, 7, with or without hearing loss

Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss is a liver disorder that presents with impaired bile flow leading to cholestasis and associated liver abnormalities. The condition is linked to changes in the USP53 gene, which plays a role in cellular functions related to liver health. It is inherited in an autosomal recessive pattern and typically presents in childhood. Although precise prevalence estimates are not available, the clinical findings are consistently observed in affected individuals.

The clinical presentation of this condition is dominated by liver-related findings. All affected individuals show consistently elevated levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase along with cholestasis and pruritus, with hepatic fibrosis being always present. In addition, some patients may experience hearing impairment (in 30-79% of cases), splenomegaly, and hypocalcemia, while a smaller subset show hepatic bridging fibrosis. Not all individuals experience all features, and severity varies considerably.

This condition arises due to pathogenic variants in the USP53 gene. It is inherited in an autosomal recessive pattern, meaning that affected individuals inherit two altered copies of the gene, one from each parent. As a result, families with a history of this condition may have a 25% recurrence risk with each pregnancy, and genetic counseling is recommended to understand the implications for family planning. Variable expressivity is noted, which means that the severity and specific symptoms can differ even among affected individuals.

Currently, management focuses on supportive care and symptom management as no treatments have received FDA approval specifically for this condition. Treatment is tailored to the individual through a multidisciplinary approach that may include pediatric hepatologists, nutrition experts, and audiologists when hearing issues are present. Regular surveillance for liver function and complications is essential, and genetic counseling is recommended to help families understand inheritance risks and management options. Patients should discuss treatment options with their healthcare team to determine which therapies may be appropriate for their specific situation.

Outcomes for individuals with cholestasis, progressive familial intrahepatic, 7, with or without hearing loss vary depending on the severity of liver involvement and access to comprehensive care. While many individuals continue to experience the characteristic features such as cholestasis, pruritus, and hepatic fibrosis, the course of the condition may include periods of stabilization interspersed with complications. Variability in symptoms is common and outcomes have improved over time with advances in supportive treatment. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with genetic counselors and healthcare specialists for personalized guidance.

Clinical trials are underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.