Cerebrotendinous xanthomatosis is an inherited genetic disorder characterized by abnormal storage of fats in many areas of the body.
Affected individuals are unable to break down certain lipids effectively, specifically different forms of cholesterol, leading to an accumulation of these fats in the form of fatty yellow nodules called xanthomas. These xanthomas are most found in the brain and in the connective tissue that connects the muscle to the bone, called tendons. The accumulation of these xanthomas in the brain can lead to neurological problems including recurrent seizures, movement disorders, impaired speech, loss of sensation in the arms and legs, decline in intellectual function, hallucinations, and depression. Early diagnosis and treatment are important with cerebrotendinous xanthomatosis as oral bile acid replacement therapy can halt disease progression or prevent symptoms from occurring in asymptomatic individuals.
This condition is caused by pathogenic (disease-causing) variants in the CPY27A1 gene. Cerebrotendinous xanthomatosis exhibits autosomal recessive inheritance, meaning both parents must be carriers to have a 25% chance of having a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Sephardic Jewish descent have a carrier frequency of 1 in 76. Carriers do not typically show any signs or symptoms of the condition. Other names for this condition include cerebral cholesterinosis and Van Bogaert-Scherer-Epstein disease.