https://pubmed.ncbi.nlm.nih.gov/39440620/ cholestasis

J Pediatr Gastroenterol Nutr. 2024 Oct 23.
doi: 10.1002/jpn3.12392. Online ahead of print.

Natural course and outcomes of children with ubiquitin-specific protease 53 (USP53)-related genetic chronic cholestasis

Seema Alam 1, Bikrant Bihari Lal 1, Aathira Ravindranath 2, Ashish Bavdekar 3, Nirmala Dheivamani 4, Pandey Snehavardhan 5, Aashay Shah 6, Parijat Ram Tripathi 7, Aabha Nagral 8 9, K P Srikanth 10, Ira Shah 11, Somashekara Hosaagrahara Ramakrishna 12, Arya Suchismita 13, Yogesh Waikar 14, Vaibhav Shah 15, Zahabiya Nalwalla 16, Karunesh Kumar 17, Arjun Maria 18, Anupam Sibal 17, Viswanathan M Sivaramakrishnan 19, Nishant Wadhwa 18, A Ashritha 1, Vikrant Sood 1, Rajeev Khanna 1; Indian PFIC Registry
Affiliations expand
PMID: 39440620

DOI: 10.1002/jpn3.12392

Abstract

Ubiquitin-specific protease 53 (USP53) is essential for formation of cellular tight junctions and variations in this gene disrupt the tight junctions, resulting in cholestasis. We describe the clinical manifestations and outcomes of patients with USP53 mutations from the Indian progressive familial intrahepatic cholestasis registry. All 29 patients who harbored mutations in the USP53 gene either in the homozygous, compound heterozygous, or heterozygous state and presented with cholestasis were included. USP53 variants related to cholestasis had good outcomes, with native liver survival in 82.7%, whereas 17.3% required liver transplantation. Jaundice developed in 93% and within 3 months of age in 48.8%. Jaundice resolved in 21 (72.4%). Pruritus 76% at a median age of 7 months (severe in 10/22, 45% and refractory to medical therapy in 4, 18.1%). Majority of them (82.7%) had biallelic mutations. Protein-truncating mutations were present in 20 (69%) and missense mutations in 9 (31%). No correlation was found between the genotype and the outcome.