Combined 3-methylglutaconic and 3-hydroxy-3-methylglutaric aciduria with endocardial fibroelastosis and dilatative cardiomyopathy in male and female siblings with partial deficiency of complex II/III in fibroblasts

被引:10
作者
Ruesch, S
Krahenbuhl, S
Kleinle, S
LiechtiGallati, S
Schaffner, T
Wermuth, B
Weber, J
Wiesmann, UN
机构
[1] UNIV BERN,SECT METAB DISORDERS,CHILDRENS HOSP,CH-3010 BERN,SWITZERLAND
[2] UNIV ZURICH,INST CLIN PHARMACOL & TOXICOL,ZURICH,SWITZERLAND
[3] UNIV HOSP BERN,DEPT CLIN CHEM,CH-3010 BERN,SWITZERLAND
[4] UNIV HOSP BERN,DEPT PATHOL,CH-3010 BERN,SWITZERLAND
[5] UNIV HOSP BERN,INST CLIN PHARMACOL,CH-3010 BERN,SWITZERLAND
关键词
organic aciduria; 3-methylglutaconic acid; 3-hydroxy-3-methylglutaric acid; dilative cardiomyopathy; respiratory chain; complex deficiency;
D O I
10.1159/000468642
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We report on 2 children, brother and sister, who presented with cardiomyopathy and muscular hypotonia at the age of 8 months. They both excreted significant amounts of 3-hydroxy-3-methylglutaric acid (3-HMG) and 3-methylglutaconic acid (3-MGC) but no 3-methylglutaric acid (3-MG). Enzyme analysis in fibroblasts revealed normal activities of 3-hydroxy-3-methylgrutaryl-CoA (HMG-CoA) lyase and of 3-methylglutaconyl hydratase and other enzymes of 3-HMG metabolism. Loading tests with leucine did not affect the excretion of 3-HMG and 3-MGC. The girl died as a result of her cardiomyopathy, while the boy recovered and was treated with cardiac supportive therapy. He showed a steady improvement during his clinical course with biochemical normalization of the urinary excretion of 3-HMG, concomitant with marked improvement in the hypertrophic cardiomyopathy. In cultured fibroblasts from both patients a reduced activity of complex II/III of the respiratory chain was measured which may be the cause of this new type of 3-HMG uria. Analysis of mitochondrial DNA heart muscle, liver and fibroblast culture of the patient did not reveal any major mitochondrial DNA rearrangements (deletion, duplication) or any point mutation that had been described in association with mitochondrial cardiomyopathy.
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页码:321 / 329
页数:9
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