The causes of lysosomal storage diseases, the organelles affected, and major sites of pathology
| Mechanism of lysosomal storage | Disease examples | Lysosomal protein defect (gene symbol) | Substrate(s) stored | Major peripheral organ systems affected | CNS pathology |
| Lysosomal enzyme deficiencies | Aspartylglucosaminuria | Aspartylglucosaminidase (glycosylasparaginase, AGA) | aspartylglucosamine (N-acetylglucosaminyl-asparagine) | Skeleton, connective tissue | + |
| Fabry | α-Galactosidase (GLA) | (Lyso-)Globotriaosylceramide | Kidney, heart | − | |
| Gaucher types 1, 2, and 3 | β-Glucocerebrosidase (GBA) | Glucosylceramide, glucosylsphingosine | Spleen/liver, bone marrow | +a | |
| GM1-gangliosidosis | β-Galactosidase (GLB1) | GM1-ganglioside, oligosaccharides | Skeleton, heart | + | |
| Krabbe (globoid cell leukodystrophy) | Galactocerebrosidase (GALC) | Galactosylceramide | Heart | + | |
| Metachromatic leukodystrophy | Arylsulfatase A (ARSA) | Sulfogalactosylceramide | + | ||
| Mucopolysaccharidoses | Enzymes involve in mucopolysaccharide catabolism | Mucopolysaccharides | Cartilage, bone, heart, lungs | +b | |
| Multiple sulfatase deficiency | SUMF1 (Formylglycine-generating enzyme needed to activate sulfatases) | Multiple, including sulfated glycosaminoglycans | Spleen/liver, bone, skin | + | |
| Pompe | α-Glucosidase (GAA) | Glycogen | Skeletal muscle | − | |
| Sandhoff | β-hexosaminidase A and B (HEXB) | GM2-ganglioside | + | ||
| Trafficking defect of lysososomal enzymes | Mucolipidosis type II (I-cell disease) | N-acetyl glucosamine phosphoryl transferase α/β (GNPTAB) | Carbohydrates, lipids, proteins | Skeleton, heart | + |
| Mucolipidosis type IIIA (pseudo-Hurler polydystrophy) | N-acetyl glucosamine phosphoryl transferase α/β (GNPTAB) | Carbohydrates, lipids, proteins | Skeleton, heart | +/− | |
| Defects in soluble non-enzymatic lysosomal proteins | Niemann-Pick disease type C2 | NPC2 (soluble cholesterol binding protein) | Cholesterol and sphingolipids | Liver | + |
| Defects in lysosomal membrane proteins | Cystinosis | Cystinosin (cysteine transporter, CTNS) | Cystine | Kidney, eye | − |
| Danon disease | Lysosomal-associated membrane protein 2, splicing variant A (LAMP2) | Glycogen and other autophagic components | Cardiac and skeletal muscle | + | |
| Free sialic acid storage disorder | Sialin (sialic acid transporter, SLC17A5) | Free sialic acid | Liver/spleen, skeleton | + | |
| Mucolipidosis IV | Mucolipin-I (MCOLN1) | Mucopolysaccharides and lipids | Eye | + | |
| Niemann-Pick disease type C1 | NPC1 (membrane protein involved in lipid transport) | Cholesterol and sphingolipids | Liver | + | |
| Enigmatic lysosomal disorders | Neuronal ceroid lipofuscinoses (NCLs, including Batten disease) | Disparate group of diseases with genetic defects in apparently unrelated genes, not all of which are associated with the lysosomal system. Not known if these genes cooperate in common cellular pathways. | Autofluorescent lipofuscin is a common feature, with convergent clinical signs, e.g., visual system defects/blindness | + |
| Mechanism of lysosomal storage | Disease examples | Lysosomal protein defect (gene symbol) | Substrate(s) stored | Major peripheral organ systems affected | CNS pathology |
| Lysosomal enzyme deficiencies | Aspartylglucosaminuria | Aspartylglucosaminidase (glycosylasparaginase, AGA) | aspartylglucosamine (N-acetylglucosaminyl-asparagine) | Skeleton, connective tissue | + |
| Fabry | α-Galactosidase (GLA) | (Lyso-)Globotriaosylceramide | Kidney, heart | − | |
| Gaucher types 1, 2, and 3 | β-Glucocerebrosidase (GBA) | Glucosylceramide, glucosylsphingosine | Spleen/liver, bone marrow | +a | |
| GM1-gangliosidosis | β-Galactosidase (GLB1) | GM1-ganglioside, oligosaccharides | Skeleton, heart | + | |
| Krabbe (globoid cell leukodystrophy) | Galactocerebrosidase (GALC) | Galactosylceramide | Heart | + | |
| Metachromatic leukodystrophy | Arylsulfatase A (ARSA) | Sulfogalactosylceramide | + | ||
| Mucopolysaccharidoses | Enzymes involve in mucopolysaccharide catabolism | Mucopolysaccharides | Cartilage, bone, heart, lungs | +b | |
| Multiple sulfatase deficiency | SUMF1 (Formylglycine-generating enzyme needed to activate sulfatases) | Multiple, including sulfated glycosaminoglycans | Spleen/liver, bone, skin | + | |
| Pompe | α-Glucosidase (GAA) | Glycogen | Skeletal muscle | − | |
| Sandhoff | β-hexosaminidase A and B (HEXB) | GM2-ganglioside | + | ||
| Trafficking defect of lysososomal enzymes | Mucolipidosis type II (I-cell disease) | N-acetyl glucosamine phosphoryl transferase α/β (GNPTAB) | Carbohydrates, lipids, proteins | Skeleton, heart | + |
| Mucolipidosis type IIIA (pseudo-Hurler polydystrophy) | N-acetyl glucosamine phosphoryl transferase α/β (GNPTAB) | Carbohydrates, lipids, proteins | Skeleton, heart | +/− | |
| Defects in soluble non-enzymatic lysosomal proteins | Niemann-Pick disease type C2 | NPC2 (soluble cholesterol binding protein) | Cholesterol and sphingolipids | Liver | + |
| Defects in lysosomal membrane proteins | Cystinosis | Cystinosin (cysteine transporter, CTNS) | Cystine | Kidney, eye | − |
| Danon disease | Lysosomal-associated membrane protein 2, splicing variant A (LAMP2) | Glycogen and other autophagic components | Cardiac and skeletal muscle | + | |
| Free sialic acid storage disorder | Sialin (sialic acid transporter, SLC17A5) | Free sialic acid | Liver/spleen, skeleton | + | |
| Mucolipidosis IV | Mucolipin-I (MCOLN1) | Mucopolysaccharides and lipids | Eye | + | |
| Niemann-Pick disease type C1 | NPC1 (membrane protein involved in lipid transport) | Cholesterol and sphingolipids | Liver | + | |
| Enigmatic lysosomal disorders | Neuronal ceroid lipofuscinoses (NCLs, including Batten disease) | Disparate group of diseases with genetic defects in apparently unrelated genes, not all of which are associated with the lysosomal system. Not known if these genes cooperate in common cellular pathways. | Autofluorescent lipofuscin is a common feature, with convergent clinical signs, e.g., visual system defects/blindness | + |