A Novel Compound Heterozygous CYP27A1 Variant in Cerebrotendinous Xanthomatosis: A Case Report from a...

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive lipid storage disorder characterized by the accumulation of cholesterol and cholestanol in various tissues. It is caused by pathogenic variants in the CYP27A1 gene, which encodes the mitochondrial enzyme sterol 27-hydroxylase.

Here, we present an 8-year-old boy with attention-deficit/hyperactivity disorder, born to non-consanguineous parents. He was referred to our center for CYP27A1 gene analysis and genetic counseling, following the identification of a homozygous deletion in exon 6 of the CYP27A1 gene in his mother. His plasma cholestanol levels were also elevated, supporting a diagnosis of CTX. The proband's father had a history of epilepsy and mild intellectual disability. Genetic analysis of the father revealed a novel heterozygous p.(Glu170Valfs*16) variant in the CYP27A1 gene. Based on these findings, the proband was found to carry a compound heterozygous variant in CYP27A1, confirming the molecular diagnosis of CTX. After genetic counseling, treatment with chenodeoxycholic acid (CDCA) was initiated. Plasma cholestanol levels normalized, and some clinical symptoms showed improvement after 2 months of treatment.

Early genetic screening of presymptomatic family members is critical, as timely initiation of CDCA therapy can prevent or significantly attenuate the clinical progression of CTX.