Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. We conclude that mevalonate kinase deficiency leads to a decreased synthesis of ubiquinone-10 and that ubiquinone-10 deficiency is responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity.
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PMID:Decreased plasma ubiquinone-10 concentration in patients with mevalonate kinase deficiency. 823 12

Mevalonic aciduria, due to mevalonate kinase deficiency, is the first recognized defect in the biosynthesis of cholesterol and isoprenoids. Very few patients with this disorder have been reported. Three siblings born from consanguineous parents are reported. Several clinical signs were present in all 3 children, including failure-to-thrive, susceptibility to infections, hepatosplenomegaly, cataract, and psychomotor retardation. Dysmorphic features were more apparent in the two older siblings. Urinary organic acid analysis by gas chromatography/mass spectrometry invariably revealed a high urinary excretion rate of mevalonic acid. Mevalonate kinase activity assayed in fibroblasts was very low. Diagnosis of this very rare disease may be suspected simply on clinical evidence; it is confirmed by abnormal excretion of mevalonic acid.
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PMID:Mevalonic aciduria in 3 siblings: a new recognizable metabolic encephalopathy. 835 61