Mucopolysaccharidosis and Its Orthopedic Manifestations – A Review

Abstract

Mucopolysaccharidosis (MPS) represents a group of rare, inherited lysosomal storage disorders characterized by defective enzymatic degradation of glycosaminoglycans (GAGs). These sulphated carbohydrate polymers are integral to cellular architecture and signaling. In MPS, deficient or malfunctioning lysosomal enzymes lead to the accumulation of undegraded GAGs—such as heparan sulphate, dermatan sulphate, and keratan sulphate—within tissues, disrupting cellular homeostasis and triggering multisystemic manifestations. Clinically, patients exhibit a spectrum of features including coarse facies, cognitive impairment, hepatosplenomegaly, hernias, joint stiffness, and corneal clouding. The disease is classified into seven major subtypes (MPS I–IV, VI, VII, IX), each defined by a unique enzymatic defect and associated GAG profile, with variable severity and inheritance patterns. Among the most debilitating aspects of MPS are skeletal complications and these include thickened calvarium, malformed vertebrae, shortened long bones, and joint contractures, often resulting in restricted mobility, chronic pain, and orthopedic deformities. Musculoskeletal complications vary among the different subtype of MPS. This review synthesizes current knowledge on skeletal manifestations in MPS, drawing from literature published since 2000.