Unidad de Enfermedades Mitocondriales y Enfermedades Metabólicas Hereditarias, Servicio de Pediatría, Hospital Universitario 12 de Octubre, CSUR Enfermedades Metabólicas, MetabERN, Instituto de Investigación Sanitaria Hospital 12 de octubre (imas12), CIBERER, Madrid, Spain.
Servicio de Medicina Interna, CSUR Enfermedades Metabólicas, MetabERN, Instituto de Investigación Sanitaria Hospital 12 de octubre (imas12), Hospital Universitario 12 de Octubre, Madrid, Spain.
Orphanet J Rare Dis. 2021 Nov 3;16(1):464. doi: 10.1186/s13023-021-02074-y.
Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL).
Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5-40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106-136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03-2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68-3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25-2.34) versus 2.25 (1.62-3.00) in patients not treated with ERT.
The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams.
黏多糖贮积症（MPS）IVA 或莫尔奎奥 A 综合征是一种进行性和致残性疾病，其特征是缺乏 N-乙酰半乳糖胺-6-硫酸酯硫酸酯酶。其临床表现在成人中非常异质且了解甚少。本研究的目的是描述西班牙成人 MPS IVA 患者的临床表现，并评估其健康相关生活质量（HRQoL）。
来自 9 个参考中心的 33 名患者参与了这项研究。中位年龄为 32 岁（四分位距 [IQR]：20.5-40.5）。54.5%的患者表现为经典表型，33.3%的患者表现为中间表型，12.1%的患者表现为非经典表型。最常见的临床表现是骨发育不良，中位身高为 118（IQR：106-136）cm。其他常见的临床表现包括听力损失（75.7%）、韧带松弛（72.7%）、齿状突发育不良（69.7%）、需要矫形辅助的肢体畸形（主要为髋关节发育不良和膝内翻）（63.6%）和角膜混浊（60.6%）。此外，36.0%的患者患有阻塞性睡眠呼吸暂停/低通气综合征，33.3%的患者需要无创通气。颈椎手术和椎体切开术是最常见的手术干预措施（各占 36.4%）。几乎 80%的患者存在活动问题，36.4%的患者始终需要轮椅。此外，87.9%的患者需要自理帮助，33.3%的患者完全依赖，78.8%的患者存在一定程度的疼痛。根据健康评估问卷，非经典表型患者的 HRQoL 为 1.43（IQR：1.03-2.00），而经典表型患者的 HRQoL 为 2.5（IQR：1.68-3.00）。7 名患者开始接受酶替代疗法（ERT）治疗，但其中 2 名患者失访。4 名患者的肺功能有所改善，1 名患者略有恶化。4 名能够进行六分钟步行测试的患者的步行距离有所增加。接受艾拉司琼治疗的患者 HRQoL 更好，中位数（IQR）为 1.75（1.25-2.34），而未接受 ERT 治疗的患者为 2.25（1.62-3.00）。
该研究提供了 MPS IVA 患者的真实世界数据。活动受限、自理困难、依赖和疼痛很常见，同时 HRQoL 也很差。临床表现的严重程度和异质性需要多学科团队的共同努力。
