Patients with MPS VI lack critical enzyme activity
MPS VI is one of a group of 7 types of mucopolysaccharidosis disorders (MPS I, II, III, IV, VI, VII and IX) that belong to a larger category of lysosomal storage disorders (LSD). Persons with LSDs lack one or more lysosomal enzymes, which can eventually lead to progressive, multisystemic disease.4,5
MPS VI is caused by an inherited deficiency in the enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B or ASB). Owing to the presence of different mutations in the gene in different patients, heterogeneity exists in the nature of the deficiency in this enzyme.8 Of note, decreased levels of ASB activity is what confirms an MPS VI diagnosis.2
ASB regulates the catabolism of a glycosaminoglycan (GAG) called dermatan sulfatan and is one of 5 enzymes necessary for stepwise degradation of dermatan sulfatan.5
- GAGs have important roles in cellular structure and cell interactions, especially in connective tissue and its extracellular matrix9
GAG accumulation in MPS VI
In the absence of ASB, partially degraded GAG accumulates in cell lysosomes,4 the organelles responsible for the breakdown of metabolites.
- Replete with excess GAG, lysosomes crowd the nucleus and other critical organelles, engorging the cell
- This leads to cellular malfunction, multisystemic organ damage and an extensive range of symptoms
Because GAG is a major constituent of the extracellular matrix of connective tissues throughout the body (eg, vessel linings, bone marrow, heart, lung, liver and spleen stromata), many organ systems are affected.9
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