Glycosaminoglycan Storage Disorders: A Review

Abstract

Impaired degradation of glycosaminoglycans (GAGs) with consequent intralysosomal accumulation of undegraded products causes a group of lysosomal storage disorders known as mucopolysaccharidoses (MPSs). Characteristically, MPSs are recognized by increased excretion in urine of partially degraded GAGs which ultimately result in progressive cell, tissue, and organ dysfunction. There are eleven different enzymes involved in the stepwise degradation of GAGs. Deficiencies in each of those enzymes result in seven different MPSs, all sharing a series of clinical features, though in variable degrees. Usually MPS are characterized by a chronic and progressive course, with different degrees of severity. Typical symptoms include organomegaly, dysostosis multiplex, and coarse facies. Central nervous system, hearing, vision, and cardiovascular function may also be affected. Here, we provide an overview of the molecular basis, enzymatic defects, clinical manifestations, and diagnosis of each MPS, focusing also on the available animal models and describing potential perspectives of therapy for each one.

Urinary Glycosaminoglycan Estimation as a Routine Clinical Service

“…These inherited disorders of metabolic defects are grouped as mucopolysaccharidoses (MPSs) [3]. There are around 8 sub categories (MPS I-MPS VIII) based on the type of enzyme defect and/or substrate/ product accumulated.…”

“…MPS IIIa-IIId result due to deficiency of four different enzymes mainly associated with degradation of heparan sulfate. Deficiency of several other enzymes are responsible for MPS type IV-VIII causing increased excretion of keratan sulfate, chondroitin sulfate and dermatan sulfate either individually or in different combinations [3]. The amount of glycosaminoglycan excreted varies in different types of MPS and is also dependent on severity of the condition.…”

Mucopolissacaridose em um cão: relato de caso

“…Mucopolissacaridose (MPS) pertence a um grupo de doenças congênitas, geradas por deficiência de enzimas lisossomais específicas, que catalizam a degradação dos glicosaminoglicanos (GAGs), geralmente presentes no tecido conjuntivo, e geram, dessa forma, acúmulo lisossomal, que culmina com disfunção de células, tecidos ou órgãos (Torres et al, 1997;Wang et al, 2011;Coutinho et al, 2012).…”

“…Existem quatro vias diferentes de degradação lisossomal dos GAGs, que são caracterizadas pelo tipo de molécula do GAG que será degradada: sulfato dermatan, sulfato heparan, sulfato queratan e sulfato condroitan (Coutinho et al, 2012).…”

Rare cases of classical Hurler-Scheie syndrome

“…[2][3][4] MPS is characterised by the spectrum of clinical manifestations including skeletal defects, respiratory and gastrointestinal complications, intellectual and ocular impairment and cardiovascular dysfunction. 5 The purpose of this article is to highlight the distinctive presentation of rare case of MPS-IH/S in two consecutive male siblings.…”