Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 and remain functional into their third and fourth decades.
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. Affected individuals demonstrate elevations of heparan sulfate in urine. Diagnostic sequencing of the NAGLU gene (MP3BZ / Mucopolysaccharidosis IIIB, Full Gene Analysis) and deletion/duplication studies are available for patients with an enzyme deficiency.
Patients with Mucolipidosis II/III (I-cell disease) may demonstrate elevations of alpha-N-acetylglucosaminidase in addition to abnormalities of other hydrolases. I-cell disease is an autosomal recessive lysosomal storage disorder resulting in impaired transport and phosphorylation of newly synthesized lysosomal proteins to the lysosome due to deficiency of N-acetylglucosamine 1-phosphotransferase (GlcNAc). Characteristic clinical features include short stature, skeletal and cardiac abnormalities, and developmental delay. Measurement of alpha-N-acetylglucosaminidase activity is not the preferred diagnostic test for I-cell disease but may be included in the testing strategy.
Preferred assay for diagnosis of Sanfilippo syndrome type B (mucopolysaccharidoses type IIIB)
Deficiency of alpha-N-acetylglucosaminidase is diagnostic for Sanfilippo syndrome type B.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This is the preferred test for diagnosing Sanfilippo syndrome type B.
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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
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. Accessed 01/13/2015. Available at www.ommbid.com
4. Neufeld EF, Muenzer J: Neufeld E.F., Muenzer J Neufeld, Elizabeth F., and Joseph Muenzer.The Mucopolysaccharidoses. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. Valle D, Beaudet A.L., Vogelstein B, Kinzler K.W., Antonarakis S.E., Ballabio A, Gibson K, Mitchell G Eds. David Valle, et al.New York, NY: McGraw-Hill; 2014. Accessed March 09, 2017. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62642135