Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management

• Published in: International journal of molecular sciences Vol. 21; no. 4; p. 1517
• Main Authors: Sawamoto, Kazuki, Álvarez González, José Víctor, Piechnik, Matthew, Otero, Francisco J, Couce, Maria L, Suzuki, Yasuyuki, Tomatsu, Shunji
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.02.2020; MDPI
• Subjects: Airway management; Bone and Bones - metabolism; Bone dysplasia; Bone surgery; bone-targeting; Bones; Cartilage; Cartilage - metabolism; Chondroitin sulfate; Chondroitin Sulfates - metabolism; Chromatography; Diagnosis; Disease; Disease Management; Early Diagnosis; Enzyme Replacement Therapy - methods; Enzymes; Extracellular matrix; galns; Genetic disorders; Genetic Therapy - methods; Genotype & phenotype; Glycosaminoglycans; Glycosaminoglycans - metabolism; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Keratan sulfate; Keratan Sulfate - metabolism; lc-ms/ms; Lesions; Lysosomes - metabolism; Metabolic disorders; mps iva; Mucopolysaccharidosis; Mucopolysaccharidosis III - genetics; Mucopolysaccharidosis III - metabolism; Mucopolysaccharidosis IV - diagnosis; Mucopolysaccharidosis IV - genetics; Mucopolysaccharidosis IV - pathology; Mucopolysaccharidosis IV - therapy; Mutation; N-Acetylglucosamine; Nanomedicine; Osteochondrodysplasias; Patients; Proteins; Quality of Life; Review; skeletal dysplasia; Skeleton; Spinal cord; Stem cell transplantation; Stem cells; tracheal reconstructive surgery; Transplantation; X-rays; GALNS; MPS IVA; LC-MS/MS; tracheal reconstructive surgery; keratan sulfate; bone-targeting; skeletal dysplasia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21041517

Mucopolysaccharidosis type IVA (MPS IVA, or Morquio syndrome type A) is an inherited metabolic lysosomal disease caused by the deficiency of the N-acetylglucosamine-6-sulfate sulfatase enzyme. The deficiency of this enzyme accumulates the specific glycosaminoglycans (GAG), keratan sulfate, and chondroitin-6-sulfate mainly in bone, cartilage, and its extracellular matrix. GAG accumulation in these lesions leads to unique skeletal dysplasia in MPS IVA patients. Clinical, radiographic, and biochemical tests are needed to complete the diagnosis of MPS IVA since some clinical characteristics in MPS IVA are overlapped with other disorders. Early and accurate diagnosis is vital to optimizing patient management, which provides a better quality of life and prolonged life-time in MPS IVA patients. Currently, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available for patients with MPS IVA. However, ERT and HSCT do not have enough impact on bone and cartilage lesions in patients with MPS IVA. Penetrating the deficient enzyme into an avascular lesion remains an unmet challenge, and several innovative therapies are under development in a preclinical study. In this review article, we comprehensively describe the current diagnosis, treatment, and management for MPS IVA. We also illustrate developing future therapies focused on the improvement of skeletal dysplasia in MPS IVA.