Cerebrotendinous Xanthomatosis

Abstract

Cerebrotendinous xanthomatosis (CTX) is a rare neurometabolic disorder with an autosomal recessive mode of inheritance. Most patients are of borderline or low intelligence from the beginning and their school performance is poor. The more specific clinical manifestations usually appear in late childhood or early adolescence, or even later. The most commonly noted early manifestations of the disease include cataracts and xanthomas of tendons, especially the Achilles tendons, but also the tendons of the quadriceps muscle, the triceps muscle and the finger extensors. During the second or third decade, neurological problems gradually become manifest with signs of cerebellar ataxia, spastic paraparesis and tetraparesis, signs of dysfunction of the posterior columns, and signs of a peripheral polyneuropathy. Tendon reflexes are generally hyperactive. Vibratory and position senses are diminished whereas the superficial sensory modalities remain relatively intact. Foot deformity, in particular pes cavus, is often noted. About 40% of the patients develop epilepsy with generalized tonic-clonic seizures. In most cases a decline of mental function occurs in the third decade but there is a large diversity in the rapidity of the decline. Changes in personality and psychiatric problems may be present. Premature atherosclerosis may lead to angina pectoris, myocardial infarction and cardiac failure. Less frequent complaints are chronic unexplained diarrhea, pharyngeal and palatal myoclonus, mask-like facies, bulbar and pseudobulbar paresis, visual loss due to optic atrophy, generalized muscular wasting, parkinsonism, bone fractures due to osteoporosis, impaired lung function due to pulmonary xanthomas, and signs of endocrine dysfunction. In untreated cases death usually occurs between the fourth and sixth decades.