Liver Transplantation Leads to Normal Neurologic Outcome in Niemann-Pick Case Report

Niemann-Pick type C has historically been considered a contraindication to liver transplantation due to neurological delays, but a recent case report suggests this thinking may be outdated.

Niemann-Pick type C (NPC) is a genetic autosomal recessive disorder that leads to cholesterol buildup in cells, affecting major organs including the liver, lungs, and brain. It is typically caused by NPC1 gene mutation, with about 5% of cases caused by NPC2 mutation, and patients with the perinatal form of NPC often do not live past 6 months of age.

Infants with NPC typically show liver and spleen inflammation from birth or a very young age and may suffer from acute liver failure, but liver transplantation has often been avoided in NPC patients due to the likelihood of rapid neurologic disease progression.

In a case report from the Northwestern University Feinberg School of Medicine, an infant with known NPC who underwent a liver transplant is doing well neurologically and from a graft perspective 5 years post transplant.

The authors note that the case study supporting NPC as a contraindication is now 35 years old. Medications like miglustat and cyclodextrin, however, have been shown to stop or reverse the neurologic disease progression previously associated with transplant in these patients and are therefore challenging the notion that NPC is a contraindication to liver transplant.

After the patient was diagnosed with NPC due to NPC1 mutation with no obvious neurologic injury at 2 months old, a multidisciplinary team decided that a liver transplant could theoretically allow him to live for 10 to 15 years. His particular disease type was found to be compound heterozygous for the I1061T and R404Q pathogenic variants in the NPC1 gene. Notably, in infants with liver failure, the decision to transplant must be made before final diagnosis in some cases.

The infant had been struggling with ascites, respiratory failure, acute renal failure, and cirrhosis with giant cell hepatitis before undergoing a whole liver transplantation. He was discharged 5 weeks post transplant after a fairly typical recovery with no need for intraoperative continuous renal replacement therapy. The patient was given standard immunosuppression, which included tacrolimus twice per day and mycophenolate mofetil once daily for the first year. He no longer required occupational therapy and was beginning to talk at 22 months old.

Five years post transplant, he is not on any experimental NPC drugs and has normal liver function, obtained normal neurological milestones, and no longer requires speech therapy. Splenomegaly still persists despite his progress.

The authors concluded that, considering this case and a Japanese series of case reports, NPC may not be the contraindication to liver transplant that it has long been assumed to be. “Our patient has normal neurologic outcomes and has normal allograft function, and this success has led to a modification in our institutional selection criteria in these cases,” they wrote.

The ability to identify the root of a patient’s disease via sequencing and the development of more advanced drugs may also positively impact the way patients with NPC and liver failure are treated.

The authors concluded, “The use of rapid genetic sequencing may allow stratification of patients based on specific genetic mutations, and the emergence of new therapeutic drugs or gene therapies may allow for improved prognosis in patients with NPC with liver failure.”


Lemoine C, Superina R, Mohammad S. Normal long-term neurologic and graft outcome after liver transplantation in an infant with Neimann-Pick type C disease. Am J Transplant. Published online August 29, 2021. doi:10.1111/ajt.16819

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