METACHROMATIC LEUKODYSTROPHY WITHOUT ARYLSULFATASE A DEFICIENCY
METACHROMATIC LEUKODYSTROPHY WITHOUT ARYLSULFATASE A DEFICIENCY
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不伴有芳基硫酸酯酶 A 缺乏的异染性脑白质营养不良
DOI：
10.1203/00006450-197910000-00021
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发表时间：
1979
影响因子：
3.6
通讯作者：
H. Kihara
中科院分区：
文献类型：
--
作者：
L. Shapiro;K. Aleck;M. Kaback;H. Itabashi;R. Desnick;N. Brand;R. Stevens;A. Fluharty;H. Kihara
摘要：近亲父母的两个兄弟姐妹患有神经系统综合征，其特征是发育迟缓、精神运动能力退化、明显痉挛和进行性中枢神经系统变性。神经传导时间明显延迟，腓肠神经活检显示明显的异染性脑白质营养不良（MLD）典型变化。通过分析尿沉渣中的糖鞘脂来记录硫酸化糖脂代谢的损害。尽管有这些发现，白细胞和培养的皮肤成纤维细胞中芳基硫酸酯酶 A 和脑苷脂硫酸酯酶的活性接近正常。然而，当完整生长的成纤维细胞负载 35SO4-硫苷脂时，观察到硫苷脂裂解的明显缺陷，与 MLD 患者中观察到的情况相当。因此，这些患者代表了一种新形式的硫苷脂贮积病——MLD，其特征是细胞匀浆中酶活性完整，但体内和完整成纤维细胞中的硫脂代谢有缺陷。推测：由于这些患者的细胞匀浆可以在去污剂存在的情况下裂解硫苷脂，而患者本身及其完整细胞则不能，因此必须援引除相关溶酶体酶活性降低之外的其他解释来解释这种贮积病。两个最合理的假设是，要么这些患者存在阻止酶和底物在适当的亚细胞位置相互作用的缺陷，要么这些患者缺少体内硫脂水解所需的推定糖蛋白“激活因子”。
Summary: Two siblings of consanguinous parents were noted to have a neurologic syndrome marked by developmental delay, regression of psychomotor performance, marked spasticity and progressive central nervous system degeneration. Markedly delayed nerve conduction times and a sural nerve biopsy which demonstrated changes typical of metachromatic leukodystrophy (MLD) were evident. Impairment of sulfated glycolipid metabolism was documented by analysis of glycospingolipid in urinary sediment. In spite of these findings, activities of arylsulfatase A and cerebroside sulfatidase in white blood cells and cultured skin fibroblasts were near normal. However, when intact growing fibroblasts were loaded with 35SO4-sulfatide a clear defect in sulfatide cleavage, comparable to that seen in MLD patients, was observed. Thus, these patients represent a new form of sulfatide storage disease – MLD characterized by intact enzyme activity in cell homogenates but defective sulfolipid metabolism in vivo and in intact fibroblasts.Speculation: Since cell homogenates from these patients can cleave sulfatide in the presence of detergents while the patients themselves and their intact cells cannot, soire explanation other than decreased activity of the relevant lysosomal enzyme must be invoked to explain this storage disease. The two most plausible hypotheses are that either these patients have a defect which prevents enzyme and substrate interaction in the proper subcellular location, or that these patients are missing the putative glycoprotein ″activating factor″ necessary for sulfolipid hydrolysis in vivo.