General description

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder caused by a mutation in the CYP27A1 gene, which is related to sterol 27-hydroxylase, an enzyme involved in bile acid biosynthesis in hepatic mitochondria. This mutation disrupts bile acid biosynthesis, leading to abnormal accumulation of cholestanol in various organs.

The clinical presentation of CTX is characterized by a wide spectrum of manifestations that vary considerably among patients. Early manifestations may include neonatal jaundice or cholestasis, chronic diarrhea in infancy, and juvenile cataracts. These initial symptoms are often nonspecific, contributing to the substantial diagnostic delay typically observed in CTX patients.

As the disease progresses, patients develop tendon xanthomas, particularly affecting the Achilles tendons, which appear as fusiform enlargements with characteristic MRI findings. Systemic manifestations include osteoporosis, premature atherosclerosis, and coronary heart disease.

The neuropsychiatric manifestations are diverse and progressively debilitating. These include cognitive impairment ranging from mild learning disabilities to dementia, cerebellar ataxia, pyramidal signs, progressive myelopathy, peripheral neuropathy, extrapyramidal manifestations such as parkinsonism and dystonia, epileptic seizures, and psychiatric symptoms.