Natural course and outcomes of children with ubiquitin‐specific protease 53 (USP53)‐related genetic chronic cholestasis
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.
Authors
- Parijat Ram Tripathi (ORCID: https://orcid.org/0000-0002-2690-3641)
- Arjun Maria
- Somashekara Hosaagrahara Ramakrishna (ORCID: https://orcid.org/0000-0001-8846-1212)
- Snehavardhan Pandey
- Ira Shah (ORCID: https://orcid.org/0000-0002-0027-0284)
- A. Ashritha
- Seema Alam (ORCID: https://orcid.org/0000-0003-0888-8625)
- Aashay Shah
- Nirmala Dheivamani (ORCID: https://orcid.org/0000-0002-2691-3559)
- Bikrant Bihari Lal (ORCID: https://orcid.org/0000-0001-6275-7736)
- Aathira Ravindranath (ORCID: https://orcid.org/0000-0001-9323-7725)
- Zahabiya Nalwalla
- Nishant Wadhwa (ORCID: https://orcid.org/0000-0001-7534-2783)
- Anupam Sibal (ORCID: https://orcid.org/0000-0002-0611-854X)
- Arya Suchismita
- Aabha Nagral (ORCID: https://orcid.org/0000-0003-0005-2508)
- Ashish Bavdekar (ORCID: https://orcid.org/0009-0006-9466-4095)
- Rajeev Khanna (ORCID: https://orcid.org/0000-0003-0800-4068)
- Yogesh Waikar
- Karunesh Kumar (ORCID: https://orcid.org/0000-0002-8121-8524)
- Vaibhav Shah (ORCID: https://orcid.org/0009-0003-2058-1578)
- Viswanathan M. Sivaramakrishnan
- Vikrant Sood
- K. P. Srikanth
Institutions
- Indraprastha Apollo Hospitals (IN)
- Apollo Hospitals (IN)
- Indira Gandhi Institute of Medical Sciences (IN)
- Niloufer Hospital (IN)
- Jaslok Hospital (IN)
- Bai Jerbai Wadia Hospital for Children (IN)
- Sir Ganga Ram Hospital (IN)
- Institute of Liver and Biliary Sciences (IN)
- Institute of Child Health (IN)
- Nethradhama Superspeciality Eye Hospital (IN)
- Sahyadri Hospital (IN)
- Manipal Hospital (IN)
Publication Details
- Journal
- Journal of Pediatric Gastroenterology and Nutrition
- Published
- 2024-10-23
- DOI
- https://doi.org/10.1002/jpn3.12392
- Citations
- 2
- Primary Topic
- Drug Transport and Resistance Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.57