NeurometPlus

Incidence

Cerebrotendinous xanthomatosis is an autosomal recessive disorder. Incidence in the USA is 1 in 72000 to 150000 births. Only several hundreds cases have been reported (condition underdiagnosed).

Clinical Characteristics

Cerebrotendinous xanthomatosis is a rare, inherited lipid-storage disease characterized clinically by progressive neurologic dysfunction (cerebellar ataxia beginning after puberty, systemic spinal cord involvement and a pseudobulbar phase leading to death), premature atherosclerosis, and cataracts. Large deposits of cholesterol and cholestanol are found in virtually every tissue, particularly the Achilles tendons, brain, and lungs. Cholestanol, the 5-alpha-dihydro derivative of cholesterol, is enriched relative to cholesterol in all tissues. The diagnosis can be made by demonstrating cholestanol in abnormal amounts in the serum and tendon of persons suspected of being affected. Plasma cholesterol concentrations are low normal in CTX patients. Cerebrotendinous xanthomatosis is an autosomal recessive disorder with juvenile onset. It becomes chronic and progresses until adulthood. Biochemically, it causes accumulation of cholestanol due to sterol 27-hydroxylase deficiency. The enzyme is implied in the synthesis of biliary acids as well as in the metabolism of other sterols with a hydroxyl group in position 27. Clinically, cataract is often the first sign. Slight mental retardation may be associated, along with a spinocerebellous syndrome and sometimes psychiatric manifestations. Psychiatric signs may also be the only symptom of the disease. Xanthomas are systematically found, usually in the calcaneal tendons, elbows and back of neck. The electromyogram evidences peripheral neuropathy, which is otherwise silent. MRI shows diffuse demyelination. The diagnosis is based on the presence of cholestanol in plasma and xanthomas. The gene is located on chromosome 2 (2q33-qter) being a mutation of CYP27A1 gene and has been cloned. Neurological and psychiatric symptoms may be prevented and reduced when the patient is treated with chenodeoxycholic acid (CDCA). Heterozygotes can be detected.

Precipitants

none

Provocation Tests

none

Diagnostic Procedures

The diagnosis can be made by demonstrating cholestanol in abnormal elevated amounts in the serum and tendons of persons suspected of being affected. Plasma cholesterol concentrations are low normal in CTX patients. Normal to slightly elevated plasma cholesterol. Elevated plasma cholestanol. Elevated urinary 7-alpha-hydroxylated bile alcohols. CTX Dx must be confirmed with testing mutation of CYP27A1 gene.