Table 1.
Neurological LSDs
Summary of neurological LSDs, including details of defective gene, primary protein involved, and associated lysosomal storage product (adapted from Platt et al.1).
| Neurological LSD (gene) | Primary defective protein (substrate/storage product) |
|---|---|
| Mucopolysaccharidoses (MPS) | |
| MPS I, also known as Hurler syndrome (IDUA) | α-L-iduronidase (dermatan sulfate, heparan sulfate) |
| MPS II (IDS) | iduronate 2-sulfatase (dermatan sulfate, heparan sulfate) |
| MPS III | |
| Type A (SGSH) | N-sulfoglucosamine sulfohydrolase (heparan sulfate) |
| Type B (NAGLU) | N-acetyl-α-glucosaminidase (heparan sulfate) |
| Type C (HGSNAT) | heparan-α-glucosaminide-N-acetyltransferase (heparan sulfate) |
| Type D (GNS) | N-acetylglucosamine-6-sulfatase (heparan sulfate) |
| MPS VII (GUSB) | β-glucuronidase (dermatan sulfate, heparan sulfate, chondroitin 6-sulfate) |
| Sphingolipidoses | |
| Fabry disease (GLA) | α-galactosidase A (globotriaosylceramide) |
| Gaucher disease type II, III, and perinatal lethal form (GBA) | β-glucocerebrosidase (glucocerebroside and glucosylsphingosine) |
| GM1 gangliosidosis types I-III (GLB1) | β-galactosidase (GM1 ganglioside, keratan sulfate, and oligosaccharides) |
| GM2 gangliosidosis | |
| Tay-Sachs (HEXA) | β-hexosaminidase (GM2 ganglioside, glycosphingolipids, and oligosaccharides) |
| Sandhoff (HEXB) | β-hexosaminidase (GM2 ganglioside, GA2 glycolipid, and oligosaccharides) |
| GM2 activator deficiency (GM2A) | GM2 ganglioside activator (GM2 ganglioside and glycosphingolipids) |
| Krabbe disease, also known as globoid cell leukodystrophy (GALC) | galactosylceramidase (galactocerebroside and psychosine) |
| Metachromatic leukodystrophy (ARSA and PSAP) | arylsulfatase A and prosaposin (sulfatides) |
| Niemann-Pick disease type A (SMPD1) | sphingomyelin phosphodiesterase (sphingomyelin) |
| Glycoproteinoses | |
| α-Mannosidosis types I, II, and III (MAN2B1) | lysosomal α-mannosidase (mannose-rich oligosaccharides) |
| β-Mannosidosis (MANBA) | β-mannosidase (Man(β1>4) N-acetylglucosamine) |
| Fucosidosis (FUCA1) | α-L-fucosidase (fucose-rich oligosaccharides, glycoproteins, and glycolipids) |
| Aspartylglucosaminuria (AGA) | aspartoglucosaminidase (aspartylglucosamine) |
| Schindler disease: types I–III (NAGA) | α-N-acetylgalactosaminidase (sialylated or asialo glycopeptides and glycosphingolipids) |
| Sialidosis type II (NEU1) | neuraminidase-1 (sialylated oligosaccharides and glycopeptides, LAMP1, and amyloid precursor protein) |
| Glycogen storage diseases (GSD) | |
| GSD II, also known as Pompe disease (GAA) | lysosomal α-glucosidase, also known as acid maltase (glycogen) |
| Lipid storage diseases | |
| Acid lipase deficiency, also known as Wolman disease (LIPA) | lysosomal acid lipase/cholesteryl ester hydrolase (cholesteryl esters, triglycerides, and other lipids) |
| Post-translational modification defects | |
| Mucolipidosis type II, also known as Inclusion-cell disease (GNPTAB) | N-acetylglucosamine-1-phosphotransferase subunits α/β (oligosaccharides, glycosaminoglycans, and glycosphingolipids) |
| Integral membrane protein disorders | |
| Danon disease (LAMP2) | lysosomal associated membrane protein 2 (cytoplasmic debris and glycogen) |
| Action myoclonus-renal failure syndrome (SCARB2) | lysosomal integral membrane protein 2 (unknown) |
| Sialic acid storage disease (SLC17A5) | sialin (sialic acids) |
| Niemann-Pick disease type C (NPC1 and NPC2) | NPC intracellular cholesterol transporter 1 and 2 (cholesterol and sphingolipids) |
| Mucolipidosis type IV (MCOLN1) | mucolipin 1 (lipids and mucopolysaccharides) |
| Neuronal ceroid lipofuscinoses (largely unknown heterogeneous mix of substrates) | |
| CLN1 (PPT1) | palmitoyl-protein thioesterase 1 (lipidated thioesters and saposins A and D) |
| CLN2 (TPP1) | tripeptidyl peptidase 1 (subunit c of mitochondrial ATP synthase) |
| CLN3 (CLN3) | battenin (subunit c of mitochondrial ATP synthase) |
| CLN4 (DNAJC5) | cysteine string protein (subunit c of mitochondrial ATP synthase) |
| CLN5 (CLN5) | ceroid-lipofuscinosis neuronal protein 5 (subunit c of mitochondrial ATP synthase) |
| CLN6 (CLN6) | transmembrane ER protein (subunit c of mitochondrial ATP synthase) |
| CLN7 (MFSD8) | major facilitator superfamily domain containing 8 (subunit c of mitochondrial ATP synthase) |
| CLN8 (CLN8) | ceroid-lipofuscinosis neuronal protein 8 (subunit c of mitochondrial ATP synthase) |
| CLN9 (gene unknown) | protein unknown (substrate unknown) |
| CLN10 (CTSD) | cathepsin D (saposins A and D) |
| CLN11 (GRN) | granulin (unknown) |
| CLN12 (ATP13A2) | cation-transporting ATPase 13A2 (inorganic cations) |
| CLN13 (CTSF) | cathepsin F (unknown) |
| CLN14 (KCTD7) | potassium channel tetramerization domain containing 7 (unknown) |
| Lysosome-related organelle disorders | |
| Chédiak-Higashi disease (LYST) | lysosomal trafficking regulator (size and movement of lysosomes) |