title: Pathophysiology of cerebrotendinous xanthomatosis.
abstract: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal-recessive lipid storage disease caused by mutations in the CYP27A1 gene, which lead to deficiency of the mitochondrial enzyme, sterol 27-hydroxylase, resulting in the accumulation of cholestanol in the serum and many affected lesions. To date, more than 50 different CYP27A1 mutations, including missense mutations, frameshifts, and splice site mutations, have been reported worldwide in patients with CTX. Clinical presentation is characterized by neonatal jaundice or cholestasis, refractory diarrhea, juvenile cataracts, tendon xanthomas, osteoporosis, coronary heart disease, and progressive neuropsychiatric disturbances; however, combinations of symptoms vary from patient to patient. Neuropsychiatric abnormalities include mental retardation or dementia, psychiatric symptoms, cerebellar signs, pyramidal signs, progressive myelopathy, peripheral neuropathy, extrapyramidal manifestations, and seizures. Replacement treatment with chenodeoxycholic acid in the early stage of the disease has been reported to improve or even prevent clinical symptoms of CTX. After significant neurological pathology is established, the effect of the treatment is limited and the deterioration of clinical manifestations may continue; therefore, early diagnosis of CTX is crucial.
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University Faculty of Medicine.
authors.forename: Shingo
authors.initials: S
authors.lastname: Koyama
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
mesh_terms: D002635:Chenodeoxycholic Acid / Q000008:administration & dosage; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D004083:Cholestanol / Q000378:metabolism; D003937:Diagnosis, Differential; D018450:Disease Progression; D042241:Early Diagnosis; D006801:Humans; D009154:Mutation; D012720:Severity of Illness Index; D019294:Xanthomatosis, Cerebrotendinous / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy
chemical_list: D002635:Chenodeoxycholic Acid; D004083:Cholestanol; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase