Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management

Abstract

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.

Characterization of New Proteomic Biomarker Candidates in Mucopolysaccharidosis Type IVA

“…A deficiency of N -acetylgalactosamine-6-sulfatase (GALNS, E.C.3.1.6.4) [ 1 , 2 , 3 ] leads to the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S) in multiple tissues, mainly bone, cartilage, heart valves, and cornea. The classical phenotype is characterized by systemic skeletal dysplasia with incomplete ossification and successive imbalance of growth [ 4 ], including short stature and neck, cervical instability, spinal cord compression, tracheal obstruction, prominent chest, kyphoscoliosis, laxity of joints, hip dysplasia, and knock knees [ 5 , 6 ]. Respiratory failure is the primary cause of death during the second and third decades of life in untreated patients [ 7 , 8 ].…”

Research and Application of Chondroitin Sulfate/Dermatan Sulfate-Degrading Enzymes

“…Enzyme replacement therapy is the standard treatment option for MPSs, which can start treatment immediately and improve prognosis. Recombinant human IDS (idursulfase and idursulfase beta), GALNS (elosulfase alfa) and ARSB (galsulfase) are clinically used to treat the corresponding MPSs (Whiteman and Kimura, 2017;Sawamoto et al, 2020;Harmatz and Shediac, 2017). Hematopoietic stem cell transplantation is also available for MPSs treatment (Coppa et al, 1995;Mullen et al, 2000).…”

Spine radiograph in dysplasias: A pictorial essay

“…[ 11 ] The beaking is in anteroinferior location in MPS type 1 (Hurler's syndrome)[ 12 and central in MPS type 4 (Morquio syndrome). [ 13 ] Other imaging findings are listed in Table 1 .…”