Last Updated: November 6, 2025
Introduction to the Lysosomal Storage Disorders
The term “lysosomal storage disorder” (LSD) encompasses a large family of inherited metabolic disorders that are associated with the pathological accumulation of improperly degraded metabolic byproducts within the lysosomes. The consequences of the lysosomal accumulation of undegraded substrates leads to a broad spectrum of clinical manifestations that depends, in part, on the specific substrate as well as the predominant tissue(s) of accumulation. The LSD are associated with a progressive manifestation of symptoms that is variable across the spectrum of LSD, and often is variable within the same characterized disease. The latter is the result of allelic heterogeneity, a term referring to the fact that a number of different mutations in the same gene can result in the same or very similar pathology.
The LSD encompass the mucopolysaccharidotic (MPS) family of diseases that are associated with the abnormal lysosomal accumulation of glycosaminoglycans. The mucolipidoses (e.g I-cell disease; mucolipidosis II) and oligosaccharidoses (e.g. aspartylglucosaminuria) constitute another family of LSD. Pompe disease, which is classically defined as a glycogen storage disease (GSD2) was one of the first diseases characterized as resulting from abnormal lysosomal accumulation of substrate, in this case glycogen. Thus, Pompe disease is both a LSD and a GSD. Another family of LSD include the diseases of sphingolipid metabolism. The neuronal ceroid lipofuscinoses (also referred to as cerebral neurolipofuscinoses) are a group of at least 14 diseases that constitute another family of LSD.
Many of the individual LSD can be classified in more than one subfamily due to the presence of the substrate for an affected enzyme in numerous types of molecules. For instance, sialidosis is classified as an oligosaccharidotic LSD as well as a sphingolipidotic LSD.
Table of the Mucopolysaccharidoses
| Disease: MPS Designation | Enzyme Defect / Gene | Affected GAG | Symptoms / Comments |
| Hurler MPS I, MPS IH (MPS1H) | α-L-iduronidase / IDUA | dermatan sulfate, heparan sulfate | corneal clouding, dysostosis multiplex, organomegaly, heart disease, dwarfism, intellectual impairment; early mortality |
| Scheie MPS I, MPS IS (MPS1S) | α-L-iduronidase / IDUA | dermatan sulfate, heparan sulfate | corneal clouding; aortic valve disease; joint stiffening; normal intelligence and life span |
| Hurler-Scheie MPS I, MPS IHS (MPS1HS) | α-L-iduronidase / IDUA | dermatan sulfate, heparan sulfate | intermediate between I H and I S |
| Hunter MPS II (MPS2) | L-iduronate-2-sulfatase / IDS | dermatan sulfate, heparan sulfate | mild and severe forms, only X-linked MPS, dysostosis multiplex, organomegaly, facial and physical deformities, no corneal clouding, intellectual impairment, death before 15 except in mild form then survival to 20 – 60 |
| Sanfilippo A MPS III, MPS IIIA (MPS3A) | heparan N-sulfatase (also called N-sulfoglucosamine sulfohydrolase / SGSH | heparan sulfate | profound intellectual deterioration, hyperactivity, skin, brain, lungs, heart and skeletal muscle are affected in all 4 types of MPS-III |
| Sanfilippo B MPS III, MPS IIIB (MPS3B) | α-N-acetyl-D-glucosaminidase / NAGLU | heparan sulfate | phenotype similar to III A |
| Sanfilippo C MPS III, MPS IIIC (MPS3C) | acetylCoA:α-glucosaminide-acetyltransferase (also called heparan-α-glucosaminide N-acetyltransferase) / HGSNAT | heparan sulfate | phenotype similar to III A |
| Sanfilippo D MPS III, MPS IIID (MPS3D) | N-acetylglucosamine-6-sulfatase [also called glucosamine (N-acetyl)-6-sulfatase] / GNS | heparan sulfate | phenotype similar to III A |
| Morquio A MPS IV, MPS IVA (MPS4A) | galactose-6-sulfatase (also called [galactosamine (N-acetyl)-6-sulfatase] / GALNS | keratan sulfate, chondroitin 6-sulfate | corneal clouding, odontoid hypoplasia, aortic valve disease, distinctive skeletal abnormalities |
| Morquio B MPS IV, MPS IVB (MPS4B) | β-galactosidase 1 / GLB1 | keratan sulfate | severity of disease similar to IV A |
| MPS V, a designation no longer used | |||
| Maroteaux-Lamy MPS VI (MPS6) | arylsulfatase B (also called N-acetylgalactosamine-4-sulfatase) / ARSB | dermatan sulfate | 3 distinct forms from mild to severe, aortic valve disease, dysostosis multiplex, normal intelligence, corneal clouding, coarse facial features |
| Sly MPS VII (MPS7) | β-glucuronidase / GUSB | heparan sulfate, dermatan sulfate, chondroitin 4-, 6-sulfates | hepatosplenomegaly, dysostosis multiplex, wide spectrum of severity, hydrops fetalis |
| MPS VIII, a designation no longer used | |||
| Mucopolysaccharidosis type IX: MPS IX (MPS9) | hyaluronoglucosaminidase-1 (hyaluronidase)/ HYAL1 | hyaluronic acids | periarticular soft tissues masses on distal extremities and digits; very rare disease; a total of 36 known pathogenic mutations as of 2025 |
| Mucopolysacchaidosis type X: MPS X (MPS10) | arylsulfatase K/ ARSK | dermatan sulfates | metaphyseal striation of the long bones; progressive hip dysplasia; very rare disease with only 10 identified cases as of 2025; a total of 3 known pathogenic mutations as of 2025 |
Table of Oligosaccharidoses
| Disease | Enzyme Deficiency | Symptoms/Comments |
| Aspartylglucosaminuria | aspartylglucosaminidase (N-aspartyl-β-glucosaminidase) | progressive intellectual impairment, delayed speech and motor development, coarse facial features |
| β-Mannosidosis | β-mannosidase | the defective β-mannosidase associated with this disease is encoded by the mannosidase beta gene (MANBA); primarily neurological defects, speech impairment |
| α-Mannosidosis | α-mannosidase | the defective α-mannosidase associated with this disease is encoded by the mannosidase alpha class 2B, member 1 gene (MAN2B1); symptoms include intellectual impairment, dystosis multiplex, hepatosplenomegaly, hearing loss, delayed speech |
| GM1 Gangliosidosis | β-galactosidase (galactosidase beta 1) | also identified as a glycosphingolipid storage disease or lysosomal storage disease |
| Sandhoff disease | β-hexosaminidases A and B | also identified as a glycosphingolipid storage disease or lysosomal storage disease |
| Sialidosis (also identified as Mucolipidosis I) | neuraminidase 1 (sialidase) | neurominidase 1 requires the accessory protein: protective protein/cathepsin A (PPCA) which is encoded by the CTSA gene; myoclonus, congenital ascites, hepatosplenomegaly, coarse facial features, delayed mental and motor development |
| Fucosidosis | α-fucosidase 1 | two primary types: type 1 and type 2; type 1 is more severe and manifest in infancy; progressive motor and mental deterioration, growth impairment, coarse facial features, recurrent sinus and pulmonary infections |
Table of the Disorders Associated with Abnormal Sphingolipid Metabolism
| Disorder | Enzyme Deficiency | Accumulating Substance | Comments/Symptoms |
| Tay-Sachs disease | β-hexosaminidase A | GM2 ganglioside | β-hexosaminidase A is a heterodimer composed of an α-subunit encoded by the HEXA gene and a β-subunit encoded by the HEXB gene; in the infantile form there is rapidly progressing psychomotor impairment, blindness, early mortality |
| Sandhoff disease | β-hexosaminidases A and B | globoside; GM2 ganglioside | β-hexosaminidase A is a heterodimer of composed of an a-subunit encoded by the HEXA gene and a β-subunit encoded by the HEXB gene; β-hexosaminidase B is a homodimer of two β-subunits encoded by the HEXB gene; the infantile form manifests with the same symptoms as Tay-Sachs; disease progresses more rapidly than Tay-Sachs |
| Tay-Sachs AB variant GM2 activator deficiency | GM2 ganglioside activator | GM2 ganglioside | the GM2 ganglioside activator protein is encoded by the GM2A gene; the infantile form manifests with the same symptoms as Tay-Sachs |
| Gaucher disease | glucocerebrosidase (glucosylceramidase beta) | glucocerebrosides | glucocerebrosidase is encoded by the glucosylceramidase beta (GBA) gene; most common form has average age of onset of 30 years; hallmark of disease is accumulation of lipid-engorged cells of the monocyte/macrophage lineage in multiple tissues |
| Fabry disease | α-galactosidase A | globotriaosylceramide; also called ceramide trihexoside (CTH) | kidney failure, skin rashes |
| Niemann-Pick diseases Types A and B Type C | sphingomyelinase NPC1 protein | sphingomyelins LDL-derived cholesterol | the sphingomyelinase that is defective in Niemann-Pick type A (NPA) and NPB is encoded by the SMPD1 (sphingomyelin phosphodiesterase 1) gene; humans express four genes with sphingomyelin phosphodiesterase activity (SMPD1, SMPD2, SMPD3, and SMPD4; type A is severe disorder with hepatosplenomegaly, severe neurological involvement leading to early death, type B is only associated with visceral involvement |
| Krabbe disease; globoid cell leukodystrophy (GLD) | galactocerebrosidase | galactocerebrosides | galactocerebrosidase is encoded by the GALC (galactosylceramidase) gene; intellectual impairment, myelin deficiency |
| GM1 gangliosidosis | β-galactosidase-1 | GM1 gangliosides | β-galacatosidase-1 is encoded by the GLB1 (galactosidase beta 1) gene; intellectual impairment, skeletal abnormalities, hepatomegaly |
| Metachromatic leukodystrophy; sulfatide lipodosis | arylsulfatase A | sulfatides | arylsulfatase A is encoded by the ARSA gene; intellectual impairment, metachromasia of nerves |
| Farber lipogranulomatosis | acid ceramidase | ceramides | acid ceramidase is encoded by the ASAH1 (N-acylsphingosine amidohydrolase 1) gene; hepatosplenomegaly, painful swollen joints |
| Sialidosis (also identified as Mucolipidosis I) | neuraminidase 1 (sialidase) | sialyloligosaccharides in glycolipids and glycoproteins | neuraminidase 1 is encoded by the NEU1 gene; action of neuraminidase 1 requires protective protein/cathepsin (PPCA) encoded by the CTSA gene; two forms: type 1 (mild) and type 2 (severe); type 2 associated with coarse facial features, intellectual impairment, dystosis multiplex |