Pathophysiology and Treatment of Lipid Abnormalities in Cerebrotendinous Xanthomatosis: An Integrative Review

Abstract

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder caused by pathogenic variants in CYP27A1, leading to a deficiency in sterol 27-hydroxylase. This defect results in the accumulation of cholestanol and bile alcohols in various tissues, including the brain, tendons and peripheral nerves. We conducted this review to evaluate lipid profile abnormalities in patients with CTX. A search was conducted in PubMed, Embase and the Virtual Health Library in January 2023 to evaluate studies reporting the lipid profiles of CTX patients, including the levels of cholestanol, cholesterol and other lipids. Elevated levels of cholestanol were consistently observed. Most patients presented normal or low serum cholesterol levels. A decrease in chenodeoxycholic acid (CDCA) leads to increased synthesis of cholesterol metabolites, such as bile alcohols 23S-pentol and 25-tetrol 3-glucuronide, which may serve as surrogate follow-up markers in patients with CTX. Lipid abnormalities in CTX have clinical implications. Cholestanol deposition in tissues contributes to clinical manifestations, including neurological symptoms and tendon xanthomas. Dyslipidemia and abnormal cholesterol metabolism may also contribute to the increased risk of atherosclerosis and cardiovascular complications observed in some CTX patients.

Surgical Treatment of Multiple Large Tuberous and Tendinous Xanthoma Secondary to Familial Hypercholesterolaemia: A Case Report

“…1,2 Among these, tuberous xanthomas are usually presented as flat or elevated plaques less than 2 centimeters in diameter, often found in patients with lipoprotein metabolic disorders. 3,4 Here, we report a rare case of successful surgical treatment for multiple large tuberous and tendinous xanthomas secondary to familial hypercholesterolaemia (FH).…”

Editorial for Brain Sciences Special Issue: “Neurogenetic Disorders across Human Life: From Infancy to Adulthood”

“…Barcelos and colleagues present a case of Bardet-Biedl Syndrome with congenital hypothyroidism and hearing loss due to compound heterozygous variants in BBS6, which is causative of Bardet-Biedl; a homozygous pathogenic variant in the stereocilin (STRC) gene associated with deafness; and a homozygous variant in the dual oxidase 2 (DUOX2) gene associated with congenital hypothyroidism [1]. Treatable genetic disorders have a significant impact on patient wellbeing, and Ribeiro and colleagues review the treatment approach for cerebrotendinous xanthomatosis, a multisystemic disease with variable neurologic involvement [5], focusing on lipid abnormalities [6]. Regarding potentially treatable disorders, Duchenne muscular dystrophy is the most common neuromuscular disease in humans, and some causative pathogenic variants offer the possibility of targeted treatment.…”