Cerebrotendinous Xanthomatosis (CTX)
by Alexander Kurz
Cerebrotendinous xanthomatosis (CTX) is a rare inherited lipid storage disease characterised clinically by 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 ( ac cholesterol derivative) are found in virtualy every tissue, particularly in the Achilles tendons, in the brain and the lung. The enzymatic defect is a deficiency of hepatic mitochondrial 26-hydroxylase.
Symptoms and course
The age of onset is variable, but symptoms usually begin in the second or third decade.
Presenting features include intellectual impairment, cataracts, extensor tendon xanthomas and signs of neurological deficit. Cerebellar ataxia, spasticity, pseudobulbar palsy and peripheral neuropathy are the common neurological manifestations.
Low intelligence or dementia is present in 70 % of the cases. In the later stages there may be evidence of a peripheral neuropathy with distal loss of pain and vibraion sense.
Occasionally patients with onset of symptoms as late as the seventh decade have been reported. The course is variable, but patients tend to become incapacitated within 5 – 15 years of onset.
Death occurs from progressive pseudobulbar paralysis or myocardial infarction, the latter resulting from the premature atherosclerosis which commonly complicates the disease.
Causes and risk factors
The disease is caused by mutation in the CYP27A1 gene, which encodes sterol 27-hydroxylase (2q33).
Pathologically the disease is characterised by xanthomatous lesions and demyelination in the cerebellar white matter,with similar but less severe lesions elsewhere in the central nervous system. The peripheral nerves may show evidence of demyelination and remyelination with the formation of "onion bulbs".
The diagnosis can be confirmed by the finding of elevated levels of cholestanol in serum, tendon, or nervous tissue. Plasma cholesteros concentrations are low normal. Cerebrospinal fluid examination may show an elevated protein content. Cranial CT characteristically shows a diffuse reduction in white matter density in the cerebral hemispheres and cerebellum.
Care and treatment
Treatment with chenodeoxycholic acid has been shown to inhibit cholestanol synthesis and may reverse neurological and intellectual deterioration.
- V M Berginer, G Salen, S Shefer: Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid. N Engl J Med 311: 1649-1652, 1984
- J H Menkes, J R Schimschok, P D Swanson: Cerebrotendinous xanthomatosis. Arch Neurol 19: 47-53, 1968
- A S Truswell, P J Pfister: Cerebrotendinous xanthomatosis. Brit Med J 1: 353-354, 1972
Last Updated: Friday 09 October 2009