A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C.

Line Modin,Paul Gissen,Anibh Das,Julian Raiman,Vicky Ng,Hanna Faghfoury,Eva Doreen Pfister,René Santer,Saikat Santra,Ulrich Baumann

doi:10.3390/children8090819

Abstract

Background: To report on clinical presentation and outcomes of children who underwent liver transplantation (LTx) and were subsequently diagnosed to have Niemann-Pick type C (NPC). Methods: Retrospective, descriptive, multi-centre review of children diagnosed with NPC who underwent LTx (2003–2018). Diagnosis was made by filipin skin test or genetic testing. Results: Nine children were identified (six centres). Neonatal acute liver failure was the most common indication for LTx (seven children). Median age at first presentation: 7 days (range: 0–37). The most prevalent presenting symptoms: jaundice (8/9), hepatosplenomegaly (8/9) and ascites (6/9). 8/9 children had a LTx before the diagnosis of NPC. Genetic testing revealed mutations in NPC1 correlating with a severe biochemical phenotype in 5 patients. All 9 children survived beyond early infancy. Seven children are still alive (median follow-up time of 9 (range: 6–13) years). Neurological symptoms developed in 4/7 (57%) patients at median 9 (range: 5–13) years following LTx. Conclusion: Early diagnosis of NPC continues to be a challenge and a definitive diagnosis is often made only after LTx. Neurological disease is not prevented in the majority of patients. Genotype does not appear to predict neurological outcome after LTx. LTx still remains controversial in NPC.

Highlights

The commonest group of known diseases causing neonatal acute liver failure (ALF)are metabolic liver disease followed by viral infections, while neonatal haemochromatosis is the single most common cause of ALF in neonates [1,2]
Niemann-Pick disease type C (NPC) is a rare multi-systemic neurodegenerative disorder caused by a defect in intracellular lipid trafficking [4]
We report on clinical presentation, morbidity and mortality of a series of children who underwent LTx and were subsequently diagnosed with Niemann-Pick type C (NPC)

Summary

Introduction

The commonest group of known diseases causing neonatal acute liver failure (ALF)are metabolic liver disease followed by viral infections, while neonatal haemochromatosis is the single most common cause of ALF in neonates [1,2]. One of the challenges in the management of neonates with ALF is the need for rapid exclusion of contraindications for liver transplantation (LTx) before clinical deterioration of the patient. In children with early onset neonatal cholestasis, the clinical cause is often more aggressive and the patient usually dies before the age of 6 months [5,6]. Neonatal presentation is commonly associated with chronic liver dysfunction This usually takes the form of a cholestatic liver disease with prolonged neonatal jaundice, often with splenomegaly [7]. We report on clinical presentation, morbidity and mortality of a series of children who underwent LTx and were subsequently diagnosed with NPC. To report on clinical presentation and outcomes of children who underwent liver transplantation (LTx) and were subsequently diagnosed to have Niemann-Pick type C (NPC)

Methods

Results

Conclusion