Abstract
Mucopolysaccharidosis type VI, or Maroteaux–Lamy syndrome, is a rare, autosomal recessive genetic disease, mainly affecting the pediatric age group. The disease is due to pathogenic variants of the ARSB gene, coding for the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB). The enzyme deficit causes a pathological accumulation of the undegraded glycosaminoglycans dermatan-sulphate and chondroitin-sulphate, natural substrates of ASB activity. Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus. Neurocognitive and behavioral abilities, commonly described as maintained, have been actually investigated by few studies. The disease, first described in 1963, has a reported prevalence between 0.36 and 1.3 per 100,000 live births across the continents. With this paper, we wish to contribute an updated overview of the disease from the clinical, diagnostic, and therapeutic sides. The numerous in vitro and in vivo preclinical studies conducted in the last 10–15 years to dissect the disease pathogenesis, the efficacy of the available therapeutic treatment (enzyme replacement therapy), as well as new therapies under study are here described. This review also highlights the need to identify new disease biomarkers, potentially speeding up the diagnostic process and the monitoring of therapeutic efficacy.
Highlights
Mucopolysaccharidosis type VI (MPS VI), or Maroteaux–Lamy syndrome (MIM# 253200), is a rare, inherited, autosomal recessive metabolic disorder caused by low to absent activity of the lysosomal enzyme N-acetylgalactosamine 4-sulfatase that catalyzes one of the steps of degradation of the glycosaminoglycans (GAGs) dermatan sulfate (DS) and chondroitin 4-sulfate (CS)
In this review we present an updated overview of the MPS VI from the clinical, diagnostic, and therapeutic sides
Feasibility of enzyme replacement therapy for MPS VI was first evaluated in vitro: the recombinant N-acetylgalactosamine 4-sulfatase enzyme obtained in CHO-DKI cells was demonstrated to be similar to the endogenous enzyme, to be able to correct the enzyme defect and to reduce GAG storage in cultured MPS VI fibroblasts [63]
Summary
Mucopolysaccharidosis type VI (MPS VI), or Maroteaux–Lamy syndrome (MIM# 253200), is a rare, inherited, autosomal recessive metabolic disorder caused by low to absent activity of the lysosomal enzyme N-acetylgalactosamine 4-sulfatase (arylsulfatase B; ASB; EC 3.1.6.12) that catalyzes one of the steps of degradation of the glycosaminoglycans (GAGs) dermatan sulfate (DS) and chondroitin 4-sulfate (CS). This leads to a progressive accumulation of these molecules into lysosomes and extracellular matrix, with consequent cell and tissue injury that progressively determines a series of multi-systems/organs failure, taking to severe clinical manifestations [1]. Retrieved publications were filtered, so as to focus on the more recent papers that were not included in the last review by Harmatz and Shediac [1]
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