Table 1.
Lysosomal storage disorders
| OMIM | Disease | Defective protein | Main storage materials |
Preliminary test |
Gene symbol |
MIM ID |
Diagnostic test |
|---|---|---|---|---|---|---|---|
| Mucopolysaccharidoses (MPSs) | |||||||
| 607014 607015 607016 |
MPS I (Hurler, Scheie, Hurler/Scheie) |
α-Iduronidase | Dermatan sulphate, heparan sulphate |
GAGs (U) | IDUA | 252800 | BGT, MGT |
| 309900 | MPS II (Hunter) | Iduronate sulphatase | Dermatan sulphate, heparan sulphate |
GAGs (U) | IDS | 309900 | BGT, MGT |
| 252900 | MPS III A (Sanfilippo A) | Heparan sulphamidase | Heparan sulphate | GAGs (U) | SGSH | 605270 | BGT, MGT |
| 252920 | MPS III B (Sanfilippo B) | Acetyl α-glucosaminidase | Heparan sulphate | GAGs (U) | NAGLU | 609701 | BGT, MGT |
| 252930 | MPS III C (Sanfilippo C) | Acetyl CoA: α-glucosaminide N-acetyltransferase |
Heparan sulphate | GAGs (U) | HGSNAT | 610453 | BGT, MGT |
| 252940 | MPS III D (Sanfilippo D) | N-acetyl glucosamine-6-sulphatase |
Heparan sulphate | GAGs (U) | GNS | 607664 | BGT, MGT |
| 253000 | MPS IVA (Morquio A) | Acetyl galactosamine-6-sulphatase |
Keratan sulphate, chondroiotin 6-sulphate |
GAGs (U) | GALNS | 612222 | BGT, MGT |
| 253010 | MPS IV B (Morquio B) | β-Galactosidase | Keratan sulphate | GAGs (U) | GLB1 | 611458 | BGT, MGT |
| 253200 | MPS VI (Maroteaux-Lamy) |
Acetyl galactosamine 4-sulphatase (arylsulphatase B) |
Dermatan sulphate | GAGs (U) | ARSB | 611542 | BGT, MGT |
| 253220 | MPS VII (Sly) | β-Glucuronidase | Dermatan sulphate, heparan sulphate, chondroiotin 6-sulphate |
GAGs (U) | GUSB | 611499 | BGT, MGT |
| 601492 | MPS IX (Natowicz) | Hyaluronidase | Hyluronan | - | HYAL1 | 607071 | BGT, MGT |
| Sphingolipidoses | |||||||
| 301500 | Fabry | α-Galactosidase A | Globotriasylceramide | - | GLA | 300644 | BGT, MGT |
| 228000 | Farber | Acid ceramidase | Ceramide | - | ASAH1 | 613468 | BGT, MGT |
| 230500 230600 230650 |
Gangliosidosis GM1 (Types I, II, III) |
GM1-β-galactosidase | GM1 ganglioside, Keratan sulphate, oligos, glycolipids |
Oligos (U) | GLB1 | 611458 | BGT, MGT |
| 272800 | Gangliosidosis GM2, Tay-Sachs |
β-Hexosaminidase A | GM2 ganglioside, oligos, glycolipids |
- | HEXA | 606869 | BGT, MGT |
| 268800 | Gangliosidosis GM2, Sandhoff |
β-Hexosaminidase A + B | GM2 ganglioside, oligos |
- | HEXAB | 606873 | BGT, MGT |
| 230800 230900 231000 |
Gaucher (Types I, II, III) |
Glucosylceramidase | Glucosylceramide | Chito+(S) | GBA | 606463 | BGT, MGT |
| 245200 | Krabbe | β-Galactosylceramidase | Galactosylceramide | - | GALC | 606890 | BGT, MGT |
| 250100 | Metachromatic leucodystrophy |
Arylsulphatase A | Sulphatides | Sulphatides (U) |
ARSA | 607574 | BGT, MGT |
| 257200 607616 | Niemann-Pick (type A, type B) |
Sphingomyelinase | Sphingomyelin | - | SMPD1 | 607608 | BGT, MGT |
| Olygosaccharidoses (glycoproteinoses) | |||||||
| 208400 | Aspartylglicosaminuria | Glycosylasparaginase | Aspartylglucosamine | Oligos (U) | AGA | 613228 | BGT, MGT |
| 230000 | Fucosidosis | α-Fucosidase | Glycoproteins, glycolipids, Fucoside-rich oligos |
Oligos (U) | FUCA1 | 612280 | BGT, MGT |
| 248500 | α-Mannosidosis | α-Mannosidase | Mannose-rich oligos | Oligos (U) | MAN2B1 | 609458 | BGT, MGT |
| 248510 | β-Mannosidosis | β-Mannosidase | Man(β1 → 4)GlnNAc | Oligos (U) | MANBA | 609489 | BGT, MGT |
| 609241 | Schindler | N-acetylgalactosaminidase | Sialylated/ asialoglycopeptides, glycolipids |
Oligos (U) | NAGA | 104170 | BGT, MGT |
| 256550 | Sialidosis | Neuraminidase | Oligos, glycopeptides | Bound SA (U), Oligos (U) |
NEU1 | 608272 | BGT, MGT |
| Glycogenoses | |||||||
| 232300 | Glycogenosis II/Pompe | α1,4-glucosidase (acid maltase) | Glycogen | CK (S) | GAA | 606800 | BGT, MGT |
| Lipidoses | |||||||
| 278000 | Wolman/CESD | Acid lipase | Cholesterol esters | - | LIPA | 613497 | BGT, MGT |
| Non-enzymatic lysosomal protein defect | |||||||
| 272750 | Gangliosidosis GM2, activator defect |
GM2 activator protein | GM2 ganglioside, oligos |
- | GM2A | 613109 | MGT |
| 249900 | Metachromatic leucodystrophy |
Saposin B | Sulphatides | Sulphatides (U) |
PSAP | 176801 | MGT |
| 611722 | Krabbe | Saposin A | Galactosylceramide | - | PSAP | 176801 | MGT |
| 610539 | Gaucher | Saposin C | Glucosylceramide | - | PSAP | 176801 | MGT |
| Transmembrane protein defect | |||||||
| Transporters | |||||||
| 269920 604369 |
Sialic acid storage disease; infantile form (ISSD) and adult form (Salla) |
Sialin | Sialic acid | Free SA (U) | SLC17A5 | 604322 | MGT |
| 219800 | Cystinosis | Cystinosin | Cystine | - | CTNS | 606272 | MGT |
| 257220 | Niemann-Pick Type C1 | Niemann-Pick type 1 (NPC1) | Cholesterol and sphingolipids |
Chito+(S) | NPC1 | 607623 | Filipin test, MGT |
| 607625 | Niemann-Pick, Type C2 | Niemann-Pick type 2 (NPC2) | Cholesterol and sphingolipids |
Chito+(S) | NPC2 | 601015 | Filipin test, MGT |
| Structural Proteins | |||||||
| 300257 | Danon | Lysosome-associated membrane protein 2 |
Cytoplasmatic debris and glycogen |
- | LAMP2 | 309060 | MGT |
| 252650 | Mucolipidosis IV | Mucolipin | Lipids | - | MCOLN1 | 605248 | MGT |
| Lysosomal enzyme protection defect | |||||||
| 256540 | Galactosialidosis | Protective protein cathepsin A (PPCA) |
Sialyloligosaccharides | Bound SA (U), Oligos (U) |
CTSA | 613111 | BGTa, MGT |
| Post-translational processing defect | |||||||
| 272200 | Multiple sulphatase deficiency |
Multiple sulphatase | Sulphatides, glycolipids, GAGs |
Sulphatides (U), GAGs (U) |
SUMF1 | 607939 | BGTb, MGT |
| Trafficking defect in lysosomal enzymes | |||||||
| 252500 252600 |
Mucolipidosis IIα/β, IIIα/β |
GlcNAc-1-P transferase | Oligos, GAGs, lipids | Oligos (U) | GNPTAB | 607840 | BGTc, MGT |
| 232605 | Mucolipidosis IIIγ | GlcNAc-1-P transferase | Oligos, GAGs, lipids | Oligos (U) | GNPTG | 607838 | BGTc, MGT |
| Polypeptide degradation defect | |||||||
| 265800 | Pycnodysostosis | Cathepsin K | Bone proteins | X-ray | CTSK | 601105 | MGT |
| Neuronal ceroid lipofuscinoses (NCLs) | |||||||
| 256730 | NCL 1 | Palmitoyl protein thioesterase (PPT1) |
Saposins A and D | Ultrastructure | PPT1 | 600722 | BGT, MGT |
| 204500 | NCL 2 | Tripeptidyl peptidase 1 (TPP1) | Subunit c of ATP synthase |
Ultrastructure | TPP1 | 607998 | BGT, MGT |
| 204200 | NCL 3 | CLN3, lysosomal transmembrane protein |
Subunit c of ATP synthase |
Ultrastructure | CLN3 | 607042 | MGT |
| 256731 | NCL 5 | CLN5, soluble lysosomal protein |
Subunit c of ATP synthase |
Ultrastructure | CLN5 | 608102 | MGT |
| 601780 | NCL 6 | CLN6, transmembrane protein of ER |
Subunit c of ATP synthase |
Ultrastructure | CLN6 | 606725 | MGT |
| 610951 | NCL 7 | CLC7, lysosomal chloride channel |
Subunit c of ATP synthase |
Ultrastructure | MFSD8 | 611124 | MGT |
| 600143 | NCL 8 | CLN8, transmembrane protein of endoplasmic reticulum |
Subunit c of ATP synthase |
Ultrastructure | CLN8 | 607837 | MGT |
| 610127 | NCL 10 | Cathepsin D | Saposins A and D | Ultrastructure | CTSD | 116840 | MGT |
Abbreviations: CK, creatine kinase; CLN, with expansion; GAGs, glysosaminoglycans; GLcNAc-1-P, with expansion; Oligos, oligosaccharides; S, serum; SA, sialic acid; U, urine; Chito, chitotriosidase
aDefect of β-galactosidase and neuraminidase and/or cathepsin A
bDecrease in some lysosomal and non-lysosomal sulphatases
cSome lysosomal hydrolase activities increased in plasma and decreased in cultured fibroblasts
†Note that 5-7 per cent of the population have a recessively inherited defect in the chitotriosidase gene, which leads to false-negative values [11].