Current and emerging treatments and surgical interventions for Morquio A syndrome: a review.
Patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) have accumulation of the glycosaminoglycans, keratan sulfate, and chondroitin-6-sulfate, in bone and cartilage, causing systemic spondyloepiphyseal dysplasia. Features include lumbar gibbus, pectus carinatum, faring of the rib cage, marked short stature, cervical instability and stenosis, kyphoscoliosis, genu valgum, and laxity of joints. Generally, MPS IVA patients are wheelchair-bound as teenagers and do not survive beyond the second or third decade of life as a result of severe bone dysplasia, causing restrictive lung disease and airway narrowing, increasing potential for pneumonia and apnea; stenosis and instability of the upper cervical region; high risk during anesthesia administration due to narrowed airway as well as thoracoabdominal dysfunction; and surgical complications. Patients often need multiple surgical procedures, including cervical decompression and fusion, hip reconstruction and replacement, and femoral or tibial osteotomy, throughout their lifetime. Current measures to intervene in disease progression are largely palliative, and improved therapies are urgently needed. A clinical trial for enzyme replacement therapy (ERT) and an investigational trial for hematopoietic stem cell transplantation (HSCT) are underway. Whether sufficient enzyme will be delivered effectively to bone, especially cartilage (avascular region) to prevent the devastating skeletal dysplasias remains unclear. This review provides an overview of historical aspects of studies on MPS IVA, including clinical manifestations and pathogenesis of MPS IVA, orthopedic surgical interventions, and anesthetic care. It also describes perspectives on potential ERT, HSCT, and gene therapy.
Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA.
Shunji
S
Tomatsu
Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA.
William G
WG
Mackenzie
Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA.
Mary C
MC
Theroux
Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA.
Robert W
RW
Mason
Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA.
Mihir M
MM
Thacker
Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA.
Thomas H
TH
Shaffer
Department of Pediatrics, Saint Louis University, St Louis, MO, USA.
Adriana M
AM
Montaño
Department of Pediatrics, Saint Louis University, St Louis, MO, USA.
Daniel
D
Rowan
Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University, St Louis, MO, USA.
William
W
Sly
Institute for the Study of Inborn Errors of Metabolism, Pontificia Universidad Javeriana, Bogotá DC, Colombia.
Carlos J
CJ
Alméciga-Díaz
Institute for the Study of Inborn Errors of Metabolism, Pontificia Universidad Javeriana, Bogotá DC, Colombia.
Luis A
LA
Barrera
Department of Pediatrics, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Yasutsugu
Y
Chinen
Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA.
Eriko
E
Yasuda
Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA.
Kristen
K
Ruhnke
Medical Education Development Center, Gifu University, Gifu, Japan.
Yasuyuki
Y
Suzuki
Department of Pediatrics, Gifu University, Gifu, Japan.
Tadao
T
Orii
GALNS; enzyme replacement therapy; gene therapy; hematopoietic stem cell transplantation; keratan sulfate; mucopolysaccharidosis IVA