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The mucopolysaccharidoses (MPS) are a group of disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans GAG). Accumulation of GAG in lysosomes interferes with normal functioning of cells, tissues, and organs resulting in the clinical features observed in MPS disorders.
Sanfilippo syndrome (MPS type III) is an autosomal recessive MPS with 4 recognized types (A-D). Each type is caused by a deficiency in 1 of 4 enzymes involved in the degradation of heparan sulfate resulting in its lysosomal accumulation. Though biochemically different, the clinical presentation of all types is indistinguishable. Sanfilippo syndrome is characterized by severe central nervous system (CNS) degeneration, but other symptoms seen in MPS, such as coarse facial features and skeletal involvement, tend to be milder. Onset of clinical features usually occurs between 2 and 6 years in a child who previously appeared normal. The presenting symptoms are most commonly developmental delay and severe behavioral problems. Severe neurologic degeneration occurs in most patients by 6 to 10 years of age, accompanied by a rapid deterioration of social and adaptive skills. Death generally occurs by age 20, although individuals with an attenuated phenotype may have a longer life expectancy.
Sanfilippo syndrome type B is due to the absence of the enzyme N-acetyl-alpha-D-glucosaminidase (alpha-hexosaminidase), caused by mutations in the NAGLU gene. Diagnostic sequencing of the NAGLU gene (MP3BZ / Mucopolysaccharidosis IIIB, Full Gene Analysis) and deletion/duplication studies are available for patients with an enzyme deficiency.
Preferred assay for diagnosis of Sanfilippo syndrome type B (mucopolysaccharidoses type IIIB)
Deficiency of alpha-N-acetylglucosaminidase is diagnostic for Sanfilippo syndrome type B.
This is the preferred test for diagnosing Sanfilippo syndrome type B; however, if fibroblasts are readily available, ANAT / Alpha-N-Acetylglucosaminidase, Fibroblasts can be used to diagnose this disorder.
This assay detects Sanfilippo syndrome type B only. The 3 other types of Sanfilippo syndrome (A, C, and D) must be ruled out independently.
This assay will not identify carrier status for Sanfilippo syndrome type B.
1. Heron B, Mikaeloff Y, Froissart R, et al: Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. Am J Med Genet A 2011;155A(1):58-68
2. Neufeld EF, Muenzer J: Chapter 136: The Mucopolysaccharidoses. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill Book Company. Available at www.ommbid.com. Accessed 01/13/2015
3. Valstar MJ, Bruggenwirth HT, Olmer R, et al: Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype. J Inherit Metab Dis 2010;33:759-767