Sanfilippo syndrome E76.2

• Incidence (all mucopolysaccharidoses): 3-4:100,000 inhabitants/year.
• Incidence (Sanfillipo's disease): 1-5:100,000 inhabitants/year.

Autosomal-recessive inherited defects of the genes for the enzymes:

heparan sulfatase (MPS type IIIA; gene locus 17q25.3)

N-acetylglucosaminidase (MPS type IIIB; gene locus: 17q21)

Acetyl-CoA-glucosamine acetyltransferase (MPS type IIIC; gene locus chromosome 14)

N-acetylglucosamine-6-sulfatase (MPS type IIID; gene locus 12q14).

All 4 enzyme defects cause the excessive lysosomal deposition of heparan sulfate in the connective tissue and especially in the CNS.

• Integument: Generalized, yellowish-whitish, hard, caked plates, usually from birth. Followed by atrophy and sclerosis of the skin and skin appendages. Often hyperhidrosis or hypertrichosis.
• Extracutaneous manifestations: bone dysplasia, hepatomegaly, intelligence defects, possibly growth disorders, joint contractures and gargoylism.

1. Beesley CE et al (2003) Sanfilippo syndrome type D: identification of the first mutation in the N-acetylglucosamine-6-sulphatase gene. J Med Genet 40: 192-194
2. Cleary MA et al (1993) Management of mucopolysaccharidosis type III Arch Dis Child 69: 403-406
3. Fraser J et al (2002) Sleep disturbance in mucopolysaccharidosis type III (Sanfilippo syndrome): a survey of managing clinicians. Clin Genet 62: 418-421
4. Sanfilippo, S J, Podosin R, Langer LO Jr, Good, RA (1963) Mental retardation associated with acid mucopolysacchariduria (heparitin sulfate type). J Pediat 63: 837-838