PAEDIATRIC LIVER TRANSPLANTATION IN TIGHT JUNCTION PROTEIN 2 (TJP 2) DEFICIENCY.

Dugar, S.; Karthikeyan, P.; Mtegha, M.; Jayaprakash, K.; Rajwal, S.

PAEDIATRIC LIVER TRANSPLANTATION IN TIGHT JUNCTION PROTEIN 2 (TJP 2) DEFICIENCY.

All Authors

Dugar, S.

Karthikeyan, P.

Mtegha, M.

Jayaprakash, K.

Rajwal, S.

LTHT Author

Dugar, Shilpa
Karthikeyan, Palaniswamy
Mtegha, Marumbo
Jayaprakash, Kavitha
Rajwal, Sanjay

LTHT Department

Leeds Children's Hospital
Children's Services
Children's Liver Unit

Publication Date

2025

Item Type

Conference Abstract

Abstract

Progressive familial intrahepatic cholestasis (PFIC) is a heterogenous group of inherited autosomal recessive disorders which is known to cause chronic cholestatic liver disease, often requiring liver transplant (LT).1 Homozygous and bi-allelic compound heterozygous mutations TJP2 protein results in TJP2 deficiency which is also known as PFIC4.2 TJP2 deficiency causes disruption of tight junctions leading to progressive chronic liver disease. Extrahepatic manifestations of TJP2 deficiency includes subdural haematomas and chronic respiratory disease. There is little evidence on the outcomes of liver transplantation in TJP2 deficiency. The objective of this study was to describe the clinicopathological features and posttransplant course of six LT recipients with TJP2 genetic mutation (PFIC 4). Data was retrospectively collected from electronic case records of children (1-18 years) with TJP2 deficiency, who underwent LT between March 2008 and December 2013. We identified 6 patients with genetically confirmed TJP2 deficiency. 4/6 patients presented with neonatal jaundice. One patient presented at 5 years of age with focal seizures and deranged Liver function tests. One patient presented with pruritus. The median (IQR) bilirubin on presentation was 108.5 (83-131.2). 3/6 patients had severe pruritus for which one patient required external biliary diversion. 4/6 patients had undergone liver transplant and the remaining 2 patients had milder phenotype and have been transitioned to adult services. All the transplanted patients were homozygous for pathogenic mutations. The median age at transplantation was 11.5 years. The outcomes of LT are listed in table 1. One patient was transferred to another centre for LT and hence no long-term data was available. All three patients under our care recovered uneventfully after LT. One patient had to undergo a re-transplant in 2017 due to recurrent cholangitis and unfortunately died of multi-organ dysfunction due to sepsis at 19 years of age. TJP2 deficiency is a rare cause of molecular cholestasis which can result in progressive endstage liver disease needing liver transplant. The severity of liver disease correlates with the type of change caused by the mutation. No functional protein leads to very severe disease requiring LT early in their life. LT experience in TJP2 deficiency is not widely reported and this case series adds to the evidence.