Cerebrotendinous xanthomatosis
Cerebrotendinous xanthomatosis is a lipid storage disorder where cholesterol and other fats accumulate in the brain and tendons, leading to neurological and physical symptoms.
Overview
Cerebrotendinous xanthomatosis is a disorder characterized by the abnormal storage of fats (lipids) in the body. Because the body cannot break down certain forms of cholesterol effectively, these fats accumulate as fatty yellow nodules called xanthomas, most commonly in the brain and tendons.
Symptoms
- Neurological Problems: Often developing in early adulthood, these include recurrent seizures (epilepsy), movement disorders, impaired speech (dysarthria), loss of sensation (peripheral neuropathy), dementia, hallucinations, and depression.
- Tendon Xanthomas: Nodules form in tendons of the hands, elbows, knees, neck, and the Achilles tendon, potentially causing discomfort and reduced flexibility.
- Other Features: Clouding of the eye lenses (cataracts), chronic diarrhea in childhood, cholestasis (reduced bile production leading to jaundice), and brittle bones prone to fracture.
- Systemic Risks: Increased risk of cardiovascular disease or respiratory failure due to lipid accumulation in the heart or lungs.
Frequency
The worldwide incidence is estimated at 1 per million individuals. It is more common in the Moroccan Jewish population, with an incidence of 1 in 108.
Causes
Mutations in the CYP27A1 gene cause this condition. This gene produces the enzyme sterol 27-hydroxylase, which is required to break down cholesterol into bile acids. Mutations lead to the production of nonfunctional enzymes, causing the accumulation of cholestanol and bile alcohols in the blood and tissues, which form the characteristic xanthomas.
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations.