Overview of Lysosomal Storage Disorders

ByMatt Demczko, MD, Mitochondrial Medicine, Children's Hospital of Philadelphia
Reviewed/Revised Mar 2024
View Patient Education

Lysosomal enzymes break down macromolecules, either those from the cell itself (eg, when cellular structural components are being recycled) or those acquired outside the cell. Inherited defects or deficiencies of lysosomal enzymes (or other lysosomal components) can result in accumulation of undegraded metabolites. Because there are numerous specific deficiencies, storage diseases are usually grouped biochemically by the accumulated metabolite. Subgroups include

See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism.

The most important are the mucopolysaccharidoses and sphingolipidoses. Type 2 glycogenosis is a lysosomal storage disorder, but most glycogenoses are not.

Because reticuloendothelial cells (eg, in the spleen) are rich in lysosomes, reticuloendothelial tissues are involved in a number of lysosomal storage disorders, but, generally, tissues richest in the substrate are most affected. Thus the brain, which is rich in gangliosides, is particularly affected by gangliosidoses, whereas mucopolysaccharidoses affect many tissues because mucopolysaccharides are present throughout the body.

Mucopolysaccharidoses (MPS)

MPS are inherited deficiencies of enzymes involved in glycosaminoglycan breakdown. Glycosaminoglycans (previously termed mucopolysaccharides) are polysaccharides abundant on cell surfaces and in extracellular matrix and structures. Enzyme deficiencies that prevent glycosaminoglycan breakdown cause accumulation of glycosaminoglycan fragments in lysosomes and cause extensive bone, soft tissue, and central nervous system changes. Inheritance is usually autosomal recessive (except for MPS type II).

Age at presentation, clinical manifestations, and severity vary by type (see table Mucopolysaccharidosis (MPS)). Common manifestations include coarse facial features, neurodevelopmental delays and regression, joint contractures, organomegaly, stiff hair, progressive respiratory insufficiency (caused by airway obstruction and sleep apnea), cardiac valvular disease, skeletal changes, and cervical vertebral subluxation.

Diagnosis of mucopolysaccharidoses is suggested by history, physical examination, bone abnormalities (eg, dysostosis multiplex) found during skeletal survey, and elevated total and fractionated urinary glycosaminoglycans. Diagnosis is confirmed by DNA analysis and/or enzyme analysis of cultured fibroblasts (prenatal) or peripheral white blood cells (postnatal). (See also testing for suspected inherited disorders of metabolism.) Additional testing is required to monitor organ-specific changes (eg, echocardiography for valvular disease, audiometry for hearing changes).

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Sphingolipidoses

Sphingolipids are normal lipid components of cell membranes; they accumulate in lysosomes and cause extensive neuronal, bone, and other changes when enzyme deficiencies prevent their breakdown. Although incidence is low, carrier rate of some forms is high.

There are many types of sphingolipidosis (see table Some Sphingolipidoses); the most common sphingolipidosis is

Others sphingolipidoses include

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Mucolipidoses and Other Lysosomal Disorders

In addition to mucolipidoses, there are many other lysosomal disorders including

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More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

  1. Online Mendelian Inheritance in Man (OMIM) database: Complete gene, molecular, and chromosomal location information

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