Identification of two Iranian siblings with cerebrotendinous xanthomatosis: a case report

Background Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder that leads to multisystem involvement. It is caused by mutations in the CYP27A1 gene which encodes the mitochondrial enzyme sterol 27-hydroxylase. Case presentation Herein we describe two affected CTX siblings with symptoms including seizures, severe diarrhea (steatorrhea), vomiting, and developmental motor delay, which was initially misdiagnosed as Short-Chain acyl-CoA dehydrogenase (SCAD) deficiency. However, to identify the possible genetic cause(s) of the disease, whole exome sequencing (WES) was performed. It was confirmed that these patients carried a nonsense variant (c.808C > T; p.Arg270Ter) of the CYP27A1 gene. The variant in the CYP27A1 gene was classified as pathogenic. Conclusion We report rare cases of CTX with a novel mutation and summarize the clinical and molecular pathogenesis of this disease. Genetic analysis should be used as the conclusive method for CTX diagnosis because of the multisystem involvement and the lack of specific symptoms. The variant in these patients expands the molecular and phenotypic basis of a variant in CTX.