Case Report: Diagnosis of Mucopolysaccharidosis Type IVA With Compound Heterozygous Galactosamine-6 Sulfatase Variants and Biopsy of Replaced Femoral Heads.

Introduction: Mucopolysaccharidosis Type IVA (MPS IVA) or Morquio A Syndrome, is a rare metabolic disorder caused by compromised galactosamine-6 sulfatase (GALNS) encoded by GALNS 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.

Methods: 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.

Results: 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 GALNS (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.

Conclusion: We have found compound heterozygous variants of GALNS . 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.