https://pubmed.ncbi.nlm.nih.gov/33414089/ Cholestasis

J Clin Lipidol. 2020 Dec 14;S1933-2874(20)30341-X. doi: 10.1016/j.jacl.2020.12.004. Online ahead of print.

Cholestasis as a dominating symptom of patients with CYP27A1 mutations: An analysis of 17 Chinese infants

Ping Zhang 1 , Jing Zhao 2 , Xiao-Min Peng 1 , Yan-Yan Qian 1 , Xue-Mei Zhao 1 , Wen-Hao Zhou 3 , Jian-She Wang 2 , Bing-Bing Wu 4 , Hui-Jun Wang 5

Abstract

Background: CYP27A1 is the disease-causing gene of cerebrotendinous xanthomatosis (CTX). As a treatable lipid storage disease, early treatment can improve the prognosis. However, CTX patients reported in the literature are mostly adult patients; the phenotype spectrum of CTX in the infantile population remains elusive.

Objective: We aimed to investigate the phenotype spectrum of infants who carried pathogenic or likely pathogenic variants in the CYP27A1 gene and were suspected of having CTX.
Methods: From June 2014 to May 2020, infants with pathogenic or likely pathogenic variants in CYP27A1 gene were enrolled, who underwent next-generation sequencing or Sanger sequencing in Children's Hospital of Fudan University. Patient characteristics, clinical treatments and outcomes were extracted from electronic medical records.

Results: A total of 17 patients with an average onset age of 8 (1-42) days were found. The average diagnosis age was ten months. Cholestasis was the dominant symptom of these infants. Thirteen variants were detected, of which c.379C > T was a hotspot variant (26.5% alleles, 9/34). Cholestatic CTX is usually underestimated, but it could be severe or even fatal in infancy. For outcomes, 5 suffered from liver failure (36%, 5/14), 1 still showed cholestasis (7%, 1/14), 7 were asymptomatic (50%, 7/14), and 1 presented seizure and developmental delay in later childhood (7%, 1/14).

Conclusion: Based on this infantile cohort, we concluded that it is necessary to consider the possibility of CTX caused by CYP27A1 gene variants for infants with cholestasis.