Abstract
Mevalonic aciduria due to mevalonate kinase deficiency is the first inherited disorder of cholesterol and nonsterol isoprene biosynthesis in man. The metabolic defect is partially counteracted by increased activities of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and the low-density-lipoprotein receptor pathway, similar to the pharmacological effects of HMG-CoA reductase inhibitors. In ten patients., we observed psychomotor retardation (10/10). hypotonia/myopathy (9/9), ataxia (5/9), failure to thrive (9/10), recurrent crises with fever/diarrhea (8/9), anemia (7/9), hepatosplenomegaly (5/10), cerebellar atrophy (5/7) dysmorphic features (5/10) and cataracts (3/10). Three patients died. The severe and diverse clinical symptoms are caused by a shortage of different end products. Ubiquinon 10, an important antioxidant, was found to be diminished in tissue samples and plasma of most patients investigated, arguing against the hypothesis that the synthesis of nonsterol isoprenes as compared to cholesterol is safely assured by high affinities of the branch-point enzymes for farnesyl pyrophosphate. The severe multisystemic pathology might be attributed to free radical pathology. Therapeutic interventions with corticosteroids ameliorated the recurrent crises. HMG-CoA reductase inhibitors may impair the biosynthesis ot nonsterol isoprenes in a fashion analogous to that observed in mevalonic aciduria
Supported by DFG (Ho 966/2-2)
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Hoffmann, G., Charpentier, C., Gibson, K. et al. MEVALONIC ACIDURIA: IMPAIRED UBIQUINON BIOSYNTHESIS AND MODEL FOR SIDE EFFECTS OF HMG-COA REDUCTASE INHIBITORS. Pediatr Res 32, 627 (1992). https://doi.org/10.1203/00006450-199211000-00136
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DOI: https://doi.org/10.1203/00006450-199211000-00136
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