Cerebrotendinous xanthomatosis (CTX) is a rare disorder caused by defect in cholesterol and bile acid metabolism. Affected patients present with cholestasis and /or chronic diarrhea in the neonatal period; cataract in the childhood (75% of the cases); brittle bones, tendon xanthomata, and brain xanthomata with neurologic dysfunction in the adulthood. Incidence of CTX is estimated to be 1/50,000 in Caucasians.
Diagnosis can be established through Mass Spectrometric analysis of urine and plasma cholesterol concentration in affected patients. Therapeutic interventions include chenodeoxycholic acid (CDCA) replacement therapy, treatment with inhibitors of HMG-CoA reductase and cataract extraction.
CTX is caused by mutations in the CYP27A1 gene, which encodes sterol 27-hydroxylase that catalyzes the mitochondrial breakdown of cholesterol to produce bile. This is a key process in maintaining the levels of cholesterol in the body. Mutations in this gene, therefore, impair the ability of the enzyme to break down cholesterol; leading to accumulation of cholestenol and cholesterol in xanthomas, blood, nerve cells, and the brain, which causes the characteristic signs of the disease.
Price Evans et al. (2007) described two Saudi siblings with premature cataract, xanthomata of the Achilles tendons, atherosclerosis and neuropsychiatric symptoms. Parents were consanguineous, and they had six other healthy children. The two patients had high cholesterol levels above the normal range, which improved after using CDCA therapy. A homozygous mutation in the CYP27A1 gene was identified in both patients. The father and two other siblings were heterozygous for the mutation.