TABLE 26.3.
Mucopolysaccharidoses Disorders
| Name | Subtype | Enzyme Deficiency | AS | Genetics | Clinical Features |
|---|---|---|---|---|---|
| MPS I | Hurler syndrome | α-l-iduronidase | DS + HS | IDUA 4p16.3 | Coarse facies, short stature, corneal clouding, joint stiffening, umbilical hernia, dysostosis multiplex, hepatosplenomegaly, frequent upper respiratory infections, cognitive impairment; death before 10 y |
| MPS I | Scheie syndrome | α-l-iduronidase | DS + HS | IDUA 4p16.3 | Hepatomegaly, joint contractures, cardiac valve abnormalities, corneal clouding; prolonged survival but with disability |
| MPS II | Hunter syndrome | Iduronate sulfatase | DS + HS | IDS Xq28 | Coarse facial features, short stature, skeletal deformities, joint stiffness, mental retardation |
| MPS III A | Sanfilippo syndrome | Heparan N-sulfatase | HS | SGSH 17q25.3 | Hirsutism, coarse facial features, behavioral problems, aggressive behavior, speech delay, hepatomegaly; most die before 20 y |
| MPS III B | Sanfilippo syndrome | α-N-acetylglucosaminidase | HS | NAGLU 17q21.2 | Cardiomegaly, coarse facial features, progressive dementia, convulsions, survive into 20s, 30s |
| MPS III C | Sanfilippo syndrome | Heparan acetyl-CoA: α-glucosaminidase N-acetyltransferase | HS | HGSNAT 8p11.21 | Delayed psychomotor development, behavioral problems, sleeping/hearing problems, coarse facial features, recurrent infection, diarrhea, epilepsy, and retinitis pigmentosa |
| MPS IV A | Morquio syndrome | Galactose-6-sulfatase | KS + CS | GALNS 16q24.3 | Musculoskeletal abnormalities, short stature, pulmonary and cardiac dysfunction, hearing loss corneal clouding; most die before 30 y |
| MPS IV B | Morquio syndrome | β-Galactosidase | KS | GLB1 3p22.3 | Musculoskeletal abnormalities, short stature, pulmonary and cardiac dysfunction, hearing loss corneal clouding; most die before 30 y |
AS, accumulated substrate; CS, Chondroitin-6-sulfate; DS, dermatan sulfate; HS, heparin sulfate; KS, keratan sulfate.
Adapted from Wraith, J. E., & Jones, S. (2014). Mucopolysaccharidosis type I. Pediatr Endocrinol Rev, 12(1), 102–106; Francisca, M., Coutinho, L., & Alves, S. (2015). From bedside to cell biology: A century of history on lysosomal dysfunction. Gene, 555(1), 50–58; Meyer, A., Kossow, K., Gal, A., et al. (2007). Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A). Pediatrics, 120(5), 1255–1261; and Morrone, A., Caciotti, A., Atwood, R., et al. (2014). Morquio A syndrome-associated mutations: A review of alterations in the GALNS gene and a new locus-specific database. Human Mutation, 35(11), 1271–1279.