Morquio-B disease: Clinical and genetic characteristics of a distinct GLB1-related dysostosis multiplex.
Morquio-B disease: Clinical and genetic characteristics of a distinct GLB1-related dysostosis multiplex.
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DOI：
10.1002/jmd2.12065
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发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Stockler-Ipsiroglu, Sylvia
中科院分区：
文献类型：
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作者：
Abumansour, Iman S;Yuskiv, Nataliya;Stockler-Ipsiroglu, Sylvia
背景：Morquio-B 病 (MBD) 是一种独特的 GLB1 相关多发性骨发育不全，累及长骨和脊柱的小梁部分，呈现 GALNS 相关 Morquio-A 病的轻度表型。方法：我们分析了 63 例（n = 62 已发表）MBD 病例，以描述其临床、生化和遗传特征。结果：51 例具有丰富临床数据的病例中，41 例为纯 MBD，包括进行性生长损伤、脊柱后侧凸、髋关节/膝外翻、关节松弛、颈椎畸形、齿状突发育不全。 51 人中有 10 人患有 MBD 以及神经病性表现，包括智力/发育/言语迟缓、痉挛、共济失调、肌张力障碍。角膜混浊、心脏瓣膜病变、肝脾肿大、脊髓受压很少见，寰枕脱位、心肌病和樱桃红斑从未报道。尿糖胺聚糖和寡糖排泄始终异常。仅使用基于 LC-MS/MS 的方法检测硫酸角质素衍生的寡糖。针对合成底物测量的残留β-半乳糖苷酶活性为0%-17%。在28个GLB1变体中，W273L（34/94等位基因）和T500A（11/94等位基因）出现最频繁。 W273L 总是与纯 MBD 相关。在 R201H 纯合子病例中也报告了纯 MBD，并且大多数病例携带 T500A 变体。纯合 Y333C 和 G438E 与 MBD 加上神经病性表现相关。在七个等位基因中观察到的 T82M、R201H 和 H281Y 先前被发现对实验伴侣敏感。 结论：数据为未来系统收集这种极其罕见疾病的临床、生化、形态和遗传数据提供了基础。
BACKGROUND: Morquio-B disease (MBD) is a distinct GLB1-related dysostosis multiplex involving the trabecular parts of long bones and spine, presenting a mild phenocopy of GALNS-related Morquio-A disease.METHODS: We analyzed 63 (n = 62 published) cases with MBD to describe their clinical, biochemical and genetic features.RESULTS: Forty-one of 51 cases with informative clinical data had pure MBD including progressive growth impairment, kyphoscoliosis, coxa/genua valga, joint laxity, platyspondyly, odontoid hypoplasia. Ten of 51 had MBD plus neuronopathic manifestations including intellectual/developmental/speech delay, spasticity, ataxia dystonia. Corneal clouding, cardiac valve pathology, hepatosplenomegaly, spinal cord compression were infrequent and atlantooccipital dislocation, cardiomyopathy and cherry red spot were never reported. Urinary glycosaminoglycan and oligosaccharide excretion was consistently abnormal. Keratan sulphate-derived oligosaccharides were only detected using LC-MS/MS-based methods. Residual beta-galactosidase activities measured against synthetic substrates were 0%-17%.Among 28 GLB1 variants, W273L (34/94 alleles) and T500A (11/94 alleles) occurred most frequently. W273L was invariably associated with pure MBD. Pure MBD also was reported in a case homozygous for R201H, and in the majority of cases carrying the T500A variant. Homozygous Y333C and G438E were associated with MBD plus neuronopathic manifestations. T82M, R201H, and H281Y, observed in seven alleles, previously have been found sensitive to experimental chaperones.CONCLUSION: Data provide a basis for future systematic collection of clinical, biochemical, morphologic, and genetic data of this ultra-rare condition.