Genetics Home Reference :
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Cerebrotendinous xanthomatosis is a disorder characterized by abnormal storage of fats (lipids) in many areas of the body. People with this disorder cannot break down certain lipids effectively, specifically different forms of cholesterol, so these fats accumulate in the body in the form of fatty yellow nodules called xanthomas. These xanthomas are most commonly found in the brain and in connective tissue called tendons that attach muscle to bone, which is reflected in the condition name (cerebro- meaning brain and -tendinous referring to tendons).
People with cerebrotendinous xanthomatosis often develop neurological problems in early adulthood that are thought to be caused by an abnormal accumulation of fats and an increasing number of xanthomas in the brain. These neurological problems include recurrent seizures (epilepsy), movement disorders, impaired speech (dysarthria), loss of sensation in the arms and legs (peripheral neuropathy), decline in intellectual function (dementia), hallucinations, and depression. Xanthomas can accumulate in the fatty substance that insulates and protects nerves (myelin), causing the destruction of myelin and disrupting nerve signaling in the brain. Degeneration (atrophy) of brain tissue caused by excess lipid deposits also contributes to the neurological problems.
Xanthomas in the tendons begin to form in early adulthood. The most common areas for xanthomas to develop are tendons in the hands, elbows, knees, neck, and in the Achilles tendon, which connects the heel of the foot to the calf muscles in the leg. Tendon xanthomas may cause discomfort and interfere with tendon flexibility. While many affected people develop tendon xanthomas, these nodules may not be easily visible underneath the skin.
Other features of cerebrotendinous xanthomatosis include clouding of the lenses of the eyes (cataracts) and chronic diarrhea in childhood; a reduced ability to produce and release a digestive fluid called bile (cholestasis), which can lead to a yellowing of the skin or whites of the eyes (jaundice); and progressively brittle bones that are prone to fracture (osteoporosis). People with cerebrotendinous xanthomatosis are also at an increased risk of developing cardiovascular disease or respiratory failure because of lipid accumulation in the heart or lungs, respectively. If untreated, the signs and symptoms related to cerebrotendinous xanthomatosis worsen over time; however, this condition varies greatly among those who are affected.
MalaCards based summary :
Cerebrotendinous Xanthomatosis, also known as
ctx, is related to
lipid storage disease and
hypercholesterolemia, familial, 1, and has symptoms including
angina pectoris,
muscle spasticity and
cerebellar ataxia. An important gene associated with Cerebrotendinous Xanthomatosis is
CYP27A1 (Cytochrome P450 Family 27 Subfamily A Member 1), and among its related pathways/superpathways are
Primary bile acid biosynthesis and
PPAR signaling pathway. The drugs
tannic acid and
Benzocaine have been mentioned in the context of this disorder. Affiliated tissues include
brain,
eye and
lung, and related phenotypes are
cataract and
intellectual disability
Disease Ontology :
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A xanthomatosis that is characterized by a deficiency in the production of the bile acid, chenodeoxycholic acid that has material basis in autosomal recessive inheritance and results in cholestanol deposition in the brain and other tissues and with elevated levels of cholesterol in plasma.
NIH Rare Diseases :
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Cerebrotendinous xanthomatosis is a disorder characterized by abnormal storage of fats (lipids) in many areas of the body (lipid storage disease ). People with this disorder cannot break down certain lipids effectively (such as cholesterol), so these fats form fatty yellow nodules called xanthomas, that accumulate in the body, especially in the brain and the tendons that attach muscle to bone, which is reflected in the condition name (cerebro- meaning brain and -tendinous referring to tendons). Symptoms may include diarrhea, clouding of the lens of the eyes (cataracts ), tendon problems and progressive neurologic problems, such as epilepsy , movement disorders, impaired speech (dysarthria ), loss of sensation in the arms and legs (peripheral neuropathy ), dementia , hallucinations, and depression. Other symptoms may include brittle bones that are prone to fracture (osteoporosis ) and an increased risk of developing heart or lung failure because of lipid buildup. It is caused by mutations in the CYP27A1 gene . Treatment may involve chenodeoxycholic acid (CDCA), inhibitors of HMG-CoA reductase, coenzyme Q10 and surgery to remove cataracts.
OMIM :
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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.
Dotti et al. (2001) examined the ophthalmologic findings of 13 CTX patients. In addition to cataracts, which were found in all cases, optic disc pallor was identified in 6 of the patients. Premature retinal senescence was also observed.
In a tabular presentation, Moghadasian et al. (2002) compared and contrasted CTX with 2 other lipid disorders with certain similarities and clinical course: familial hypercholesterolemia (see 143890) and sitosterolemia (see 210250).
(213700)
KEGG :
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Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid-storage disorder caused by deficient activity of CYP27A1 and characterized by formation of xanthomatous lesions in many tissues, particularly the brain, the lens of the eye, and tendons.
UniProtKB/Swiss-Prot :
73
Cerebrotendinous xanthomatosis: Rare sterol storage disorder characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts.
Wikipedia :
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Cerebrotendinous xanthomatosis also called cerebral cholesterosis, is an autosomal recessive form of...
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Rare neurological diseases 
