Schafer I A, Sullivan J C, Svejcar J, Kofoed J, Robertson W V
J Clin Invest. 1968 Feb;47(2):321-8. doi: 10.1172/JCI105727.
Fibroblasts from patients with Hurler syndrome retain a distinctive biochemical phenotype when grown in culture which is characterized by increased synthesis of both nonsulfated and sulfated glycosaminoglycans. Ascorbic acid reinforces the phenotypic expression of the biochemical abnormality, producing not only increased synthesis of sulfated glycosaminoglycans, but selective retention of sulfated glycosaminoglycans within the cell. Although the synthesis of nonsulfated glycosaminoglycans is also increased, these compounds, particularly hyaluronic acid are not retained by the cell but are secreted into the medium. Analyses of urine from patients with Hurler syndrome show increased absolute concentrations of nonsulfated glycosaminoglycans in addition to the expected increase in sulfated glycosaminoglycans. This indicates that the biochemical phenotype as defined in cell culture is not an artifact of the experimental model but reflects the biochemical defect in the patient. Redefinition of the biochemical defect to include nonsulfated as well as sulfated glycosaminoglycans contradicts explanations of this disease which are based on a single structural gene mutation.
黏多糖贮积症Ⅰ型（Hurler综合征）患者的成纤维细胞在培养时会保持一种独特的生化表型，其特征是未硫酸化和硫酸化的糖胺聚糖合成均增加。抗坏血酸会强化这种生化异常的表型表达，不仅会使硫酸化糖胺聚糖的合成增加，还会使硫酸化糖胺聚糖在细胞内选择性潴留。虽然未硫酸化糖胺聚糖的合成也会增加，但这些化合物，尤其是透明质酸不会被细胞潴留，而是会分泌到培养基中。对黏多糖贮积症Ⅰ型患者尿液的分析表明，除了硫酸化糖胺聚糖预期的增加外，未硫酸化糖胺聚糖的绝对浓度也增加。这表明在细胞培养中定义的生化表型不是实验模型的人为现象，而是反映了患者的生化缺陷。将生化缺陷重新定义为包括未硫酸化以及硫酸化的糖胺聚糖，这与基于单个结构基因突变对该疾病的解释相矛盾。
