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

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.

The Liver and Lysosomal Storage Diseases: From Pathophysiology to Clinical Presentation, Diagnostics, and Treatment

“…However, it needs to be highlighted that NPC diagnosis was made after LTX in eight out of nine patients. Seven children were still alive (a median follow-up time of 9 (range: 6–13) years), while neurological symptoms developed in four out of seven patients at a median of 9 (range: 5–13) years following LTx [ 67 ]. Yamada et al reported three patients with neonatal-onset NPC in whom LTx was performed as a life-saving procedure.…”

The Genetics of Inherited Cholestatic Disorders in Neonates and Infants: Evolving Challenges

“…It has also allowed for a molecular diagnosis to be obtained in patients with liver disease of an otherwise uncertain cause; the ability to obtain a diagnosis in these cases can ensure that appropriate therapies are instituted while therapies which do not offer benefit are avoided. For instance, liver transplantation is not generally associated with favourable outcomes in conditions such as mitochondrial deoxyribonucleic acid (DNA) depletion syndrome [37,38] or NPC [39]. A brief description of past, current and emerging sequencing methods is provided in Figure 1.…”