Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States; Department of Biological Sciences, University of Delaware, Newark, DE, United States.
Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
Mol Genet Metab. 2018 Sep;125(1-2):18-37. doi: 10.1016/j.ymgme.2018.05.004. Epub 2018 May 15.
Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an autosomal recessive disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to the accumulation of specific glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS), which are mainly synthesized in the cartilage. Therefore, the substrates are stored primarily in the cartilage and its extracellular matrix (ECM), leading to a direct impact on bone development and successive systemic skeletal spondylepiphyseal dysplasia. The skeletal-related symptoms for MPS IVA include short stature with short neck and trunk, odontoid hypoplasia, spinal cord compression, tracheal obstruction, obstructive airway, pectus carinatum, restrictive lung, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. The degree of imbalance of growth in bone and other organs and tissues largely contributes to unique skeletal dysplasia and clinical severity. Diagnosis of MPS IVA needs clinical, radiographic, and laboratory testing to make a complete conclusion. To diagnose MPS IVA, total urinary GAG analysis which has been used is problematic since the values overlap with those in age-matched controls. Currently, urinary and blood KS and C6S, the enzyme activity of GALNS, and GALNS molecular analysis are used for diagnosis and prognosis of clinical phenotype in MPS IVA. MPS IVA can be diagnosed with unique characters although this disorder relates closely to other disorders in some characteristics. In this review article, we comprehensively describe clinical, radiographic, biochemical, and molecular diagnosis and clinical assessment tests for MPS IVA. We also compare MPS IVA to other closely related disorders to differentiate MPS IVA. Overall, imbalance of growth in MPS IVA patients underlies unique skeletal manifestations leading to a critical indicator for diagnosis.
黏多糖贮积症 IVA（MPS IVA，Morquio A 综合征）是一种常染色体隐性遗传疾病，由 N-乙酰半乳糖胺-6-硫酸酯酶缺乏引起。这种酶的缺乏导致特定糖胺聚糖（GAGs）、硫酸软骨素 6-硫酸盐（C6S）和硫酸角质素（KS）的积累，这些物质主要在软骨中合成。因此，底物主要储存在软骨及其细胞外基质（ECM）中，直接影响骨骼发育和随后的系统性骨骼脊椎骨骺发育不良。MPS IVA 的骨骼相关症状包括身材矮小、短颈和短躯干、齿状突发育不全、脊髓压迫、气管阻塞、气道阻塞、鸡胸、限制性肺病、脊柱侧凸后凸、扁骨、髋内翻、膝内翻、蹒跚步态和关节松弛。骨骼和其他器官和组织生长失衡的程度在很大程度上导致了独特的骨骼发育不良和临床严重程度。MPS IVA 的诊断需要临床、放射学和实验室检查来得出完整的结论。为了诊断 MPS IVA，已经使用的总尿 GAG 分析存在问题，因为其值与年龄匹配对照重叠。目前，尿和血 KS 和 C6S、GALNS 酶活性以及 GALNS 分子分析用于 MPS IVA 的临床表型诊断和预后。尽管这种疾病在某些特征上与其他疾病密切相关，但 MPS IVA 可以通过其独特特征进行诊断。在这篇综述文章中，我们全面描述了 MPS IVA 的临床、放射学、生化和分子诊断以及临床评估测试。我们还将 MPS IVA 与其他密切相关的疾病进行了比较，以区分 MPS IVA。总的来说，MPS IVA 患者的生长失衡导致了独特的骨骼表现，这是诊断的关键指标。
