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.
Highlights
Mucopolysaccharidosis type IVA (MPS IVA, so-called Morquio syndrome type A) (OMIM 253000) is an autosomal recessive inherited disorder and one of the common lysosomal diseases (LSDs), caused by the deficiency of lysosomal hydrolase, N-acetylglucosamine-6-sulfate sulfatase (GALNS) enzyme (EC 3.1.6.4) [1,2,3,4]
A universal method is through a chemical reaction that manifests itself in a colorimetric manner, where the detection of GAG is due to the union of nonspecific across disulfide bridges with the dimethylmethylene blue (DMB) [54]
MPS IVA is characterized by severe systemic skeletal dysplasia, subsequent airway obstruction, spinal cord compression, and cardiovascular disease, which are often life-threatening issues for patients with this disorder
Summary
Mucopolysaccharidosis type IVA (MPS IVA, so-called Morquio syndrome type A) (OMIM 253000) is an autosomal recessive inherited disorder and one of the common lysosomal diseases (LSDs), caused by the deficiency of lysosomal hydrolase, N-acetylglucosamine-6-sulfate sulfatase (GALNS) enzyme (EC 3.1.6.4) [1,2,3,4] The deficiency of this enzyme accumulates glycosaminoglycans (GAG) such as keratan sulfate (KS) and chondroitin-6-sulfate (C6S) in multiple tissues, mainly bone, cartilage, heart valves, and cornea, leading to devastating skeletal dysplasia with incomplete ossification and successive imbalance of growth [2,5,6]. Conventional enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are currently available for patients with MPS IVA; there is no definitive therapy for providing a critical impact on bone and cartilage lesions [14,15,16]. We provide an update on ERT, HSCT, and surgical interventions for patients with MPS IVA and describe the current situation of developing new therapeutic options, including gene therapy and novel enzyme therapies
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