Ma Yiyang, Peng Hao, Hsiang Fuchou, Fang Haoyu, Du Dajiang, Jiang Chenyi, Wang Yehui, Chen Chun, Zhang Changqing, Gao Yun
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, China.
Front Pediatr. 2022 Jul 4;10:914889. doi: 10.3389/fped.2022.914889. eCollection 2022.
Mucopolysaccharidosis Type IVA (MPS IVA) or Morquio A Syndrome, is a rare metabolic disorder caused by compromised galactosamine-6 sulfatase (GALNS) encoded by gene (NM_000512.5), leading to keratin sulfate (KS), and chondroitin-6-sulfate accumulation in various organs. We present a 17-year-old woman with progressive bilateral hip pain and radiographic evidence of spondyloepiphyseal dysplasia.
Diagnosis of MPS IVA was made based on whole-exome sequencing (WES) of blood samples collected from the patient and family members, high urinary glycosaminoglycan excretion, supportive clinical manifestations, radiographic examinations, including whole-body X-rays, cervical MRI, and pelvic CT. The patient underwent bilateral total hip arthroplasties sequentially, at a 1-month interval. Femoral heads were preserved for the micro-CT (μCT) analysis and the osteochondral histology examination.
The patient presented with multiple skeletal deformities, including vertebras and long bone deformities. WES disclosed compound heterozygous variants at exon 11 (c.1156C>T) and exon 12 (c.1288C>G) of the (NM_000512.5). The μCT analysis revealed significant bone quantity loss and microarchitectural change in both weight-bearing area (WBA) and non-weight-bearing area (NWBA) of the femoral heads, while histological analysis showed structural abnormity of articular cartilage in the WBA of the femoral heads.
We have found compound heterozygous variants of . This is also the first study to report the microarchitectural and histological changes of both subchondral bone and articular cartilage of the femoral head in a patient with MPS IVA.
IVA型黏多糖贮积症（MPS IVA）或Morquio A综合征，是一种罕见的代谢性疾病，由基因（NM_000512.5）编码的半乳糖胺-6-硫酸酯酶（GALNS）功能受损引起，导致硫酸角质素（KS）和硫酸软骨素-6在各个器官中蓄积。我们报告一名17岁女性，患有进行性双侧髋关节疼痛，并伴有脊椎骨骺发育不良的影像学证据。
基于对患者及其家庭成员采集的血液样本进行全外显子组测序（WES）、高尿糖胺聚糖排泄、支持性临床表现、影像学检查（包括全身X线、颈椎MRI和骨盆CT），诊断为MPS IVA。患者在1个月的间隔内依次接受了双侧全髋关节置换术。保留股骨头用于显微CT（μCT）分析和骨软骨组织学检查。
患者出现多种骨骼畸形，包括椎骨和长骨畸形。WES揭示了基因（NM_000512.5）第11外显子（c.1156C>T）和第12外显子（c.1288C>G）的复合杂合变异。μCT分析显示股骨头的负重区（WBA）和非负重区（NWBA）均有明显的骨量丢失和微结构改变，而组织学分析显示股骨头WBA的关节软骨结构异常。
我们发现了基因的复合杂合变异。这也是首次报道MPS IVA患者股骨头软骨下骨和关节软骨的微观结构和组织学变化的研究。
