Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sterol storage disorder cerebrotendinous xanthomatosis (CTX) is characterized by abnormal deposition of cholesterol and cholestanol in multiple tissues. Deposition in the central nervous system leads to neurological dysfunction marked by dementia, spinal cord paresis, and cerebellar ataxia. Deposition in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. In two unrelated patients with CTX, we have identified different point mutations in the gene (CYP27) encoding sterol 27-hydroxylase, a key enzyme in the bile acid biosynthesis pathway. Transfection of mutant cDNAs into cultured cells results in the synthesis of immunoreactive sterol 27-hydroxylase protein with greatly diminished enzyme activity. We have localized the CYP27 gene to the q33-qter interval of human chromosome 2, and to mouse chromosome 1, in agreement with the autosomal recessive inheritance pattern of CTX. These findings underscore the essential role played by sterols in the central nervous system and suggest that mutations in other sterol metabolizing enzymes may contribute to diseases with neurological manifestations.
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PMID:Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. 201 2

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disease caused by mutations in the cytochrome P450(27) (CYP27) gene. This disease is characterized by the accumulation of a bile alcohol, cholestanol, in diverse tissues. Accumulation in the central nervous system leads to neurological dysfunction including dementia, spinal cord paresis, and cerebellar ataxia. Accumulation in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. In a Japanese family with CTX, we identified two points mutations in the CYP27 gene at different sites. One is a novel transversion, which substitutes G for C at Pro 368 (CCC) to Arg (CGC). The other is a transition, which substitutes A for G at Arg441 (CGG) to Gln (CAG), this being the same mutation that Kim et al. reported (1994. J. Lipid Res. 35: 1031 - 1039). Allele-specific polymerase chain reaction analysis indicated that the father and mother of this family, who themselves had no clinical manifestations of CTX, had the former and latter mutations heterozygously, respectively. On the other hand, the patients each had both mutations heterozygously. These results are highly suggestive, but not conclusive, that the newly identified transversion in the CYP27 gene accounts for the sterol 27-hydroxylase (EC 1.14.13.15) deficiency in these patients.
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PMID:A novel mutation in the cytochrome P450(27) (CYP27) gene caused cerebrotendinous xanthomatosis in a Japanese family. 872 24

A 39 year old patient with cerebellar signs, juvenile cataracts, and dull normal intelligence had cerebrotendinous xanthomatosis without tendon xanthomas, diagnosed previously as Marinesco-Sjoegren syndrome. Cerebrotendinous xanthomatosis was proved by a greatly increased excretion of bile alcohols in the patient's urine. Cerebrotendinous xanthomatosis is a sterol storage disorder due to an autosomal recessive inherited defect of sterol 27-hydroxylase characterised by high cholestanol concentration in multiple tissues. If tendon xanthomas are not present, a diagnosis of cerebrotendinous xanthomatosis will often not be made, unless biochemical tests are performed. The clinical features of cerebrotendinous xanthomas strongly resembles Marinesco-Sjoegren syndrome. Marinesco-Sjoegren syndrome is a autosomal recessive disorder characterised by the triad cerebellar ataxia, congenital cataract, and mental retardation. Although a late onset after the first decade of life favours cerebrotendinous xanthomatosis as the underlying disease, a definite distinction between cerebrotendinous xanthomatosis without tendon xanthomas and Marinesco-Sjoegren syndrome based on clinical presentation may be difficult. It is considered that some patients with Marinesco-Sjoegren syndrome reported in the medical literature had cerebrotendinous xanthomatosis without tendon xanthomas. This is of crucial clinical relevance, because, by contrast with Marinesco-Sjoegren syndrome, treatment for cerebrotendinous xanthomatosis is already available.
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PMID:Cerebrotendinous xanthomatosis without tendon xanthomas mimicking Marinesco-Sjoegren syndrome: a case report. 877 69

Cerebrotendinous xanthomatosis (CTX) OMIM#213700 is a rare disorder of bile acid synthesis caused by deficiency of the enzyme sterol 27-hydroxylase. It results in deficiency of bile acids and accumulation of abnormal bile alcohols and accelerated cholesterol synthesis. CTX usually presents in the second or third decade with slowly progressive neurological dysfunction, cerebellar ataxia and premature atherosclerosis. Treatment with bile acid supplementation improves but does not completely reverse the neurological signs and symptoms. However, CTX is now known to be associated with a period of neonatal cholestasis. If it is diagnosed at this point, treatment may prevent the onset of neurological problems. We present the case histories and developmental findings in two affected siblings treated from infancy. We plan to continue regular neurodevelopmental reviews.
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PMID:Prospective treatment of cerebrotendinous xanthomatosis with cholic acid therapy. 1912 50

Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease caused by sterol 27-hydroxylase (CYP27) deficiency. We report three CTX siblings that shared a novel mutation of the CYP27A1 gene. These siblings presented with elevated cholestanol levels and typical manifestations such as tendon xanthomas, cataracts, osteopenia, mental retardation, cerebellar ataxia and peripheral neuropathy. All shared the same genetic mutation, c.1146_1151delins and c.1214G>A of CYP27A1. All were treated with 750 mg/day chenodeoxycholic acid (CDCA). In conclusion, one should consider the possibility of CTX in any individual with normocholesterolemic xanthomatosis, early-onset cataracts, mental retardation, cerebellar ataxia and peripheral neuropathy.
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PMID:Three siblings with Cerebrotendinous Xanthomatosis: a novel mutation in the CYP27A1 gene. 2195 93

Cerebrotendinous xanthomatosis is a rare, autosomal-recessive, lipid-storage disease with accumulation of cholestanol in most tissues, particularly within the Achilles tendons. It has been characterized both clinically and biochemically, and recently from the molecular biological aspect as well. Juvenile cataract, childhood diarrhea, mental retardation, cerebellar ataxia, and tendon xanthomas are the most prominent features of this disease. Bilateral symmetrical firm masses of Achilles tendons may be the first symptom the patient recognizes because it can jeopardize his or her ability to walk. However, the treatment strategies for tendon tumors vary. In a recent case, we diagnosed the disease properly, according to the clinical manifestations and the radiological and laboratory examinations. The genetic mutation was characterized by analyzing sterol 27-hydroxylase from the patient's family (located on nucleotide 599) and led to a nonsense mutation. It is a unique type of mutation that has never been reported to our knowledge. Tendon lesions are characterized by the loss of muscle fibers and accumulation of lipid products. To help the patient regain the strength of the Achilles tendon and walking abilities, a large area of tendon tumor was excised, followed by reconstruction with a tibialis posterior allograft, which is the second strongest tendon in the foot and ankle. Although the use of this type of graft is uncommon, the final result was satisfactory. At the 10-month follow-up examination, the patient could walk easily without pain. This case report suggests that the surgical procedure will provide an alternative for the repair of large-area degenerative Achilles tendons.
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PMID:Bilateral Achilles tendon enlargement. 2214 19

We describe our encounter with a 39-year-old man who exhibited acute painless visual loss and progressive gait disturbance. He had tendinous xanthoma and several neuroophthalmological findings indicative of optic neuropathy in the right eye, including afferent pupillary defect, cecocentral scotoma, and optic disc swelling. Neurological examination showed cerebellar ataxia and pyramidal weakness. Brain magnetic resonance imaging revealed bilateral swelling in the optic nerves with gadolinium-enhancement suggesting optic neuritis, an enlarged fourth ventricle, atrophy of the cerebellum, and hyperintensities in the bilateral dentate nuclei. The patient was diagnosed with cerebrotendinous xanthomatosis (CTX) based on an elevated serum cholestanol level and a homozygous missense mutation in CYP27A1. CTX is a genetic lipid storage disease caused by dysfunction of the mitochondrial enzyme sterol 27-hydroxylase. With respect to ophthalmological manifestations, juvenile cataracts and optic neuropathy are common findings in patients with CTX, but there have been no reports of optic neuropathy with features suggestive of optic neuritis. Thus, this case illustrates that clinicians should consider a diagnosis of CTX in patients with cardinal features of CTX even if the patients show signs indicative of optic neuritis.
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PMID:Optic Neuropathy with Features Suggestive of Optic Neuritis in Cerebrotendinous Xanthomatosis. 3089 21