Glycosaminoglycan Storage Disorders: A Review

Table 1

Summary table of mucopolysaccharidoses.

Pathology	Subtype	Enzyme deficiency	Gene (localization)	Affected GAG	Clinical manifestations	Animal model
MPS I	Hurler (H)	α-L-iduronidase		Dermatan and heparan sulfate	Corneal clouding; dysostosis multiplex; organomegaly; heart disease; mental retardation; death in childhood.	Feline [5]; canine [6]; knock-out mouse [7]
	Hurler -Scheie (H/S)	α-L-iduronidase	IDUA 4p16.3	Dermatan and heparan sulfate	Intermediate phenotype, between MPS IH and MPS IS.
	Scheie (S)	α-L-iduronidase		Dermatan and heparan sulfate	Corneal clouding; stiff joints; normal intelligence and life span.
MPS II	Hunter	Irudonate sulfatase	IDS Xq28	Dermatan and heparan sulfate	Dysostosis multiplex; organomegaly; no corneal clouding; mental retardation; death before 15 years (severe); Short stature; normal intelligence; survival to 20s to 60s (mild)	Canine [8]; knock-out mouse [9]
MPS III	Sanfilippo A	Heparan-N-sulfatase	SGSH 17q25.3	Heparan sulfate	Relatively mild somatic manifestations; hyperactivity; profound mental deterioration.	Canine [10]; spontaneous mouse mutant [11]
	Sanfilippo B	α-N-Acetylglucosaminidase	NAGLU 17q21	Heparan sulfate	Phenotype similar to MPS IIIA.	Canine [12]
	Sanfilippo C	Heparan acetyl-CoA:α-glucosaminide N-acetyltransferase	HGSNAT 8p11.1	Heparan sulfate	Phenotype similar to MPS IIIA.
	Sanfilippo D	N-Acetylglucosamine 6-sulfatase	GNS 12q14	Heparan sulfate	Phenotype similar to MPS IIIA.	Caprine [13]
MPS IV	Morquio A	Galactose 6-sulfatase	GALNS 16q24.3	Keratan and chondroitin sulfate	Distinctive skeletal abnormalities; corneal clouding; odontoid hypoplasia; milder forms known to exist.	Mouse [14]
	Morquio B	β-galactosidase	GLB1 3p21.33	Keratan sulfate	Phenotype similar to MPS IVA, with the same spectrum of severity.
MPS V	*This designation is no longer used; the phenotype, which was first classified as MPS V, was found to be the milder form of MPS I (Scheie syndrome)*
MPS VI (Maroteaux-Lamy)		Arylsulfatase B (N-acetylglucosamine 4-sulfatase)	ARSB 5q11-q13	dermatan sulfate	Dysostosis multiplex; corneal clouding; normal intelligence; survival to teens in severe form; milder forms also documented.	Feline [15]
MPS VII (Sly)		β-glucuronidase	GUSB 7q21.11	dermatan, keratan and chondroitin sulfate	Dysostosis multiplex; hepatomegaly; wide spectrum of severity including fetal hydrops and neonatal form.	Canine [16]; spontaneous mouse mutant [17]; mouse [18]
MPS VIII	*The designation MPS VIII was based on incorrect data and is no longer used.*
MPS IX		Hyaluronidase 1	HYAL 3p21.3			Mouse [19]