Liver transplantation in an infant with cerebrotendinous xanthomatosis, cholestasis, and rapid evolution of liver failure

Pediatr Transplant. 2022 Sep;26(6):e14318. doi: 10.1111/petr.14318.

PMID: 35633129

Andrea Pietrobattista, Marco Spada, Manila Candusso

Highlights: This article presents an instance of cerebrotendinous xanthomatosis (CTX) manifest as neonatal cholestasis (NC) and requiring liver transplantation (LT).

Abstract

Background: Biallelic mutations in CYP27A1 cause the bile acid (BA) metabolism condition known as cerebrotendinous xanthomatosis (CTX). As a result, cholesterol and cholestanol accumulate in a variety of tissues, which might cause neurologic disease in adults or older children. It is uncommon for neonatal cholestasis (NC) to manifest as CTX; nevertheless, if it does, liver transplantation (LT) may be necessary.

Methods: This article discusses a case of CTX manifesting as NC and necessitating LT in the context of related reports.

Results: A 4-month-old girl with normal serum gamma-glutamyl transpeptidase activity had her NC evaluated. No cause was found despite a thorough diagnostic investigation that included a liver biopsy. Rapid liver disease development requires LT aged 5 months. The explanted liver displayed micronodular cirrhosis and hepatocyte loss. The ABCB11-encoded bile salt export pump (BSEP) was not visible using immunohistochemistry. Both severe ABCB11 disease and NR1H4 disease were taken into account since NR1H4 encodes the farsenoid-X receptor, which is required for ABCB11 transcription. However, CTX was discovered to be homozygous for the CYP27A1 variant c.646G > C p.(Ala216Pro), which is predicted to be pathogenic, by selected liver disorder panel sequencing and mass spectrometry urinary BA profiling. There was no evidence of variation in any additional genes linked to intrahepatic cholestasis. The liver biopsy specimen's immunohistochemical analysis revealed a clear lack of CYP27A1 expression, while BSEP expression was unremarkable. The girl, who is 2 years old, has no neurological disorders.

Conclusions: Disorders of bile acid synthesis ought to be routinely considered as part of the NC/"neonatal hepatitis" work-up. Genetic analysis, immunohistochemical analysis, and BA profiling—a mutually supporting triple approach—might be the most effective way to diagnose CTX, a curable disease with a wide range of clinical manifestations.

Keywords: CYP27A1, bile acid synthesis disorders, cerebrotendinous xanthomatosis, liver transplantation, neonatal cholestasis