Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity
Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity
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DOI：
10.1016/j.ymgme.2004.03.001
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发表时间：
2004-06-01
影响因子：
3.8
通讯作者：
Gahl, WA
中科院分区：
文献类型：
--
作者：
Kleta, R;Morse, RP;Gahl, WA
等位基因常染色体隐性溶酶体贮积障碍Salla病和婴儿游离唾液酸贮积病（ISSD）是由SLC17A5突变引起的。该基因编码唾液素，这是一种溶酶体膜蛋白，可将带电荷的糖n -乙酰神经氨酸（唾液酸）从溶酶体中转运出去。ISSD具有严重的表型，患儿发病，而芬兰变体Salla病具有较轻的表型，发病较晚。这两种疾病都会导致发育迟缓，ISSD在儿童早期通常是致命的。我们描述了一名30个月大的非芬兰人高加索儿童，其产后发育迟缓，语言和运动技能停滞在3-4个月的水平，张力低下，面部特征轻度但进行性粗化。尿中游离唾液酸排泄量比对照高4.5倍。皮肤活检电镜显示继发性溶酶原增多，与低聚糖储存一致。成纤维细胞中游离唾液酸为3.8 +/- 0.9 nmol/rng蛋白（同期正常对照为0.5 +/- 0.1）；差速离心显示溶酶体位置。基因组分析显示两个新的SLC17A5突变具有复合杂合性。这名儿童的临床表现为溶酶体无唾液酸积存病，与她的唾液素突变和生化结果一致。出生后发育迟缓的鉴别诊断应包括游离唾液酸储存障碍，如ISSD和Salla病。Elsevier Inc.出版。
The allelic autosomal recessive lysosomal storage disorders Salla disease and infantile free sialic acid storage disease (ISSD) result from mutations in SLC17A5. This gene codes for sialin, a lysosomal membrane protein that transports the charged sugar, N-acetyl-neuraminic acid (sialic acid), Out Of lysosomes. ISSD has a severe phenotype with infantile onset, while the Finnish variant, Salla disease, has a milder phenotype with later onset. Both disorders cause developmental delay, and ISSD is generally fatal in early childhood. We describe a 30-month old non-Finnish, Caucasian child with global developmental delay of postnatal onset, language, and motor skills stagnant at a 3-4 month level, hypotonia, and mild but progressive coarsening of facial features. Urinary excretion of free sialic acid was elevated 4.5 times above control. EM of a skin biopsy revealed enlarged secondary lysosornes consistent with oligosaccharide storage. Free sialic acid in fibroblasts was 3.8 +/- 0.9 nmol/rng protein (concurrent normal controls, 0.5 +/- 0.1); differential centrifugation indicated a lysosomal location. Genomic analysis revealed compound heterozygosity for two new SLC17A5 mutations. This child's clinical manifestations of a lysosomal free sialic acid storage disease are consistent with her sialin mutations and biochemical findings. The differential diagnosis of postnatal developmental delay should include free sialic acid storage disorders such as ISSD and Salla disease. Published by Elsevier Inc.