AUTHOR=Ma Yiyang , Peng Hao , Hsiang Fuchou , Fang Haoyu , Du Dajiang , Jiang Chenyi , Wang Yehui , Chen Chun , Zhang Changqing , Gao Yun 

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

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.914889

DOI=10.3389/fped.2022.914889

ISSN=2296-2360

ABSTRACT=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 (C6S) accumulation in various organs. We present a 17-year-old female 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 GAG excretion, supportive clinical manifestations, radiographic examinations including whole-body X-rays, cervical MRI and pelvic CT. Patient underwent bilateral total hip arthroplasties (THAs) sequentially, with a one-month interval. Femoral heads were preserved for micro-CT (μCT) analysis and osteochondral histology examination. 
Results
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). 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 femoral head in a MPS IVA patient.