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Mucopolysaccharidoses: Clinical features and diagnosis

Robert Wynn, MD, MRCP, FRCPath
Section Editors
Sihoun Hahn, MD, PhD
Marc C Patterson, MD, FRACP
Deputy Editor
Elizabeth TePas, MD, MS


The mucopolysaccharidoses (MPS) are lysosomal storage disorders caused by the deficiency of enzymes required for the stepwise breakdown of glycosaminoglycans (GAGs), previously known as mucopolysaccharides [1-5]. Fragments of partially degraded GAGs accumulate in the lysosomes, resulting in cellular dysfunction and clinical abnormalities. These are rare conditions, with an estimated total incidence of all types of MPS of approximately 1 in 20,000 live births. The clinical features and diagnosis of the MPS are reviewed here. The management of these disorders is discussed separately. (See "Mucopolysaccharidoses: Complications and management".)


Glycosaminoglycans (GAGs) are large, complex polymers of linear repeating sulfated acidic and amino sugar disaccharide units attached to a protein core. They are widely distributed in many tissues where they play important roles. As examples, they are components of the ground substance of bone and cartilage, lubricant in joint fluid, and the surface coating that initially binds growth factors to cells.

The metabolic recycling of GAGs requires the stepwise degradation of the terminal sulfate, acidic, and amino sugar residues by a series of lysosomal enzymes. The deficiency of one of these enzymes blocks degradation of the substrate and results in a specific disorder. The clinical phenotype of the disorder depends upon the distribution and turnover of the substrate affected by the deficiency, rather than the distribution of the enzyme.


The mucopolysaccharidoses (MPS) disorders are classified as types I (three subtypes), II, III, IV, VI, VII, and IX. MPS V (formerly Scheie syndrome) and MPS VIII are no longer recognized. The MPS disorders are differentiated clinically by their clinical features and age of presentation and biochemically by their associated enzyme deficiency. They can be grouped into four broad categories according to their dominant clinical features (table 1):

Soft tissue storage and skeletal disease with or without brain disease (MPS I, II, VII)


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