Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in the WRN DNA helicase. It is characterized by the graying and loss of hair, juvenile cataracts, sclerosis and ulceration of skin, insulin-resistant diabetes mellitus, dyslipidemia, abdominal adiposity, osteoporosis, atherosclerosis, and malignant neoplasm. Patients are usually diagnosed in their 30s or 40s, but the early pathophysiology of the syndrome is still not fully understood. Here we report a 29-year-old female patient who displayed cataracts, hair graying, and tendinous calcinosis. Her parents were first cousins. Interestingly, the patient lacked the metabolic signs typical for WS, including glucose intolerance, dyslipidemia, and visceral fat accumulation. A hyperinsulinemic response at 30 min was observed in an oral glucose tolerance test. Mutational analysis for the WRN gene revealed a homozygous nucleotide substitution 3190C>T in exon 24, resulting in a protein product with replacement of an arginine residue at position 573 by termination codon (Arg987Ter). The mutated WRN protein was unable to translocate into the nucleus in an in vitro cell assay. A WS patient with an Arg987Ter mutation has been previously reported in Switzerland, the present case is the first to be identified in Asia. This case demonstrates the early clinical features of WS and suggests that metabolic abnormality, including insulin resistance, is not an essential component of WS at disease onset. Moreover, a follow-up study of such case would be useful to understand how the various clinical symptoms in WS develop and progress over the years.
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PMID:A case of Werner syndrome without metabolic abnormality: implications for the early pathophysiology. 2218 95

Degenerative aortic stenosis (DAS) is the most frequently diagnosed heart valve disease in Europe and North America. DAS is a chronic progressive disease which resembles development of atherosclerosis. Endothelial dysfunction, lipid infiltration, calcification and ossification are evidenced in both diseases. The same risk factors such as older age, male sex, smoking, and elevated levels of lipids are identified. The effect of smoking, visceral obesity, metabolic syndrome, hypercholesterolemia, low-density lipoprotein, high-density lipoprotein, lipoprotein(a), adiponectin and apolipoprotein(a) on development of DAS are being studied. The search for genetic ties between disorders of lipid metabolism and DAS has been started. DAS is characterized by a long symptom-free period which can last for several decades. Aortic valve replacement surgery is necessary when the symptoms occur. The lipid-lowering therapy effect on stopping or at least slowing down the progression of DAS was studied. However, the results of the conducted clinical trials are controversial. In addition, calcium homeostasis, bone metabolism and calcinosis-reducing medication are being studied. Although prospective randomized clinical trials have not demonstrated any positive effect of statins used for slowing progression of the disease, statins are still recommended for patients with dyslipidemia. Recent study has suggested that a specific modification of treatment, based on severity of disease, may have a beneficial effect in patients with aortic sclerosis and mild DAS. New clinical studies analyzing new treatment possibilities which could correct the natural course of the disease and reduce the need for aortic valve replacement by surgery or transcatheter treatment interventions are needed.
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PMID:Degenerative Aortic Stenosis, Dyslipidemia and Possibilities of Medical Treatment. 3034 55