Progressive neurologic deterioration and renal failure due to storage of glutamyl ribose-5-phosphate.
Progressive neurologic deterioration and renal failure due to storage of glutamyl ribose-5-phosphate.
复制标题
由于谷氨酰核糖-5-磷酸的储存导致进行性神经功能恶化和肾功能衰竭。
DOI：
10.1056/nejm198407193110305
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
S. Conley
中科院分区：
文献类型：
--
作者：
J. Williams;I. Butler;H. Rosenberg;R. Verani;C. Scott;S. Conley
一名六岁男孩出现癫痫史、进行性神经恶化和蛋白尿。体格检查显示轻度粗糙的外观，不能茁壮成长，全身低眼压伴肌肉萎缩，视神经萎缩；没有器质性肿大。家族史提示为X连锁隐性遗传。脑电、视网膜电信号、诱发电位和计算机轴位断层扫描均异常。已知的贮积性疾病的尿寡糖层析、尿氨基酸和有机酸、白细胞和成纤维细胞溶酶体酶分析结果均正常，但结膜和肾活检标本在电子显微镜下可见溶酶体增大。患者神经功能进行性恶化，8岁死于肾功能衰竭。从大脑(0.96摩尔/克，湿重)和肾脏(0.60摩尔/克，湿重)中提纯了一种被鉴定为谷氨酰核糖-5-磷酸的化合物。该化合物是蛋白质ADP-核糖化的连接基，是基因表达和DNA修复的重要调节过程。我们认为，这种新的疾病代表了一种糖蛋白沉积症，导致谷氨酰核糖-5-磷酸的细胞质储存。
A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 mumol per gram, wet weight) and kidney (0.60 mumol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate.