Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple sulfatase deficiency is an inherited disorder characterized by a deficiency of several sulfatases and the accumulation of sulfatides, glycosaminoglycans, sphingolipids, and steroid sulfates in tissues and body fluids. The clinical manifestations represent the summation of two diseases: late infantile metachromatic leukodystrophy and mucopolysaccharidosis. We present a 9-year-old girl with a phenotype similar to a mucopolysaccharidosis: short stature, microcephaly, and mild facial dysmorphism, along with dysphagia, retinal degeneration, developmental arrest, and ataxia. We discuss the importance of measuring the sulfatase activities in the leukocytes, and the instability of sulfatases in the cultured skin fibroblasts.
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PMID:Multiple sulfatase deficiency. 289 61

Recent treatment strategies have been directed toward blockade of estrogen action or inhibition of estrogen biosynthesis as a means of inducing regression of hormone-dependent breast cancer. The major source of estrogen in postmenopausal women is the peripheral conversion of androstenedione to estrone through the enzyme aromatase. It is known that aromatase activity increases proportionately with degree of obesity in women. To test the importance of this modulatory factor, we correlated body weight with estrogen excretion in our population of patients with breast cancer and found significant relationships. In situ production of estradiol from plasma precursors within breast cancer tissue may provide another source of estrogen. Major enzymes mediating estrogen biosynthesis were found to be present in tumor biopsy specimens. Aromatase activity was found to be present in 48/61 human tumors, sulfatase in 35/35, and 17 beta -hydroxysteroid dehydrogenase in 41/41. One inhibitor of aromatase, aminoglutethimide, has been extensively studied in patients with breast cancer. The additional effects of this drug on cholesterol side-chain cleavage and on 11-hydroxylase activity require coadministration of replacement glucocorticoid in treatment regimens. In pilot trials, 37% of patients experienced objective tumor regression with a combination of 1000 mg aminoglutethimide and 40 mg hydrocortisone daily. In randomized clinical trials with this regimen, aromatase inhibition with aminoglutethimide produced tumor regression with similar frequency as did surgical hypophysectomy, surgical adrenalectomy, or tamoxifen administration. The side effects of aminoglutethimide, including lethargy, skin rash, and ataxia complicate its use even though these problems are generally transient. Regimens of low-dose aminoglutethimide are being developed to reduce these side effects. Low-dose aminoglutethimide appears to block aromatase effectively and to have limited side effects, and is undergoing extensive clinical trial. A more specific aromatase inhibitor, 4-hydroxyandrostenedione, is now also being tested clinically, whereas MDL 18962, another new selective inhibitor, is undergoing study in animals.
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PMID:Inhibition of aromatase as treatment of breast carcinoma in postmenopausal women. 354 61

Spinocerebellar ataxia type15 (SCA15) is a pure ataxia characterized by very slow progression. Only seven families have been identified worldwide, in which partial deletions and a missense mutation of the inositol triphosphate receptor type I gene (ITPR1) have been reported. We examined a four-generation Italian family segregating an autosomal dominant cerebellar ataxia, in which linkage analysis was positive for the SCA15 locus. We performed a genomic real-time polymerase chain reaction to search for ITPR1 gene deletions in this family and in 60 SCA index cases negative for mutations in the SCA1-3, 6-8, 10, 12,and dentatorubral-pallidoluysian atrophy genes. The deleted segments were characterized using a custom array comparative genomic hybridization analysis. We have identified two families with an ITPR1 gene deletion: in one, the deletion involved ITPR1 only, while in the other both sulfatase-modifying factor 1 and ITPR1. Clinical data of ten patients and brain MRI (available for six) showed that the phenotype substantially overlapped known SCA15 cases,but we also noted buccolingual dyskinesias, facial myokymias,and pyramidal signs never reported in SCA15. ITPR1 expression analysis of two deleted cases showed a half dose. Our results further support ITPR1 gene as causative of SCA15. The families reported show that SCA15 is present in Italy and has a greater variability in the age at onset and clinical features than previously reported. We propose that the search for ITPR1 deletions is mandatory in the clinical hypothesis of SCA15 and that ITPR1-reduced expression in blood may be a useful marker to identify SCA15 patients harboring genomic deletions and possibly point mutations causing reduction of mRNA level.
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PMID:Two Italian families with ITPR1 gene deletion presenting a broader phenotype of SCA15. 2008 66