Mucopolysaccharidosis IIIB, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Mucopolysaccharidosis type III (MPS-III), also known as Sanfilippo syndrome, is an autosomal recessive condition that consists of 4 different types (A, B, C, and D). Each type of MPS-III results from the absence of 1 of 4 lysosomal enzymes, which leads to the lysosomal accumulation of heparan sulfatase. Mucopolysaccharidosis type IIIB (MPS-IIIB), or Sanfilippo syndrome B, is caused by mutations in the NAGLU gene and is characterized by reduced or absent activity of the N-acetyl-alpha-D-glucosaminidase. This test screens for mutations in all 6 exons of the NAGLU gene.
Sanfilippo syndrome is characterized by severe central nervous system degeneration with only mild physical disease. Onset of clinical features, most commonly behavioral problems and delayed development, usually occurs between 2 and 6 years in a child who previously appeared normal. 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 the 20s.
Carrier testing of individuals with a family history of mucopolysaccharidosis type IIIB
Diagnostic confirmation of mucopolysaccharidosis type IIIB when familial mutations within the NAGLU gene have been previously identified
All detected alterations will be evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order MP3BS/61818 Mucopolysaccharidosis IIIB, Full Gene Analysis.
Analysis is performed only for the provided familial mutations. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with metabolic disease.
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
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.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008;10(4):294-300
2. Valstar MJ, Ruijter GJ, van Diggelen OP, et al: Sanfilippo syndrome: a mini-review. J Inherit Metab Dis 2008;31(2):240-252
3. Yogalingam G, Hopwood JJ: Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: Diagnostic, clinical, and biological implications. Hum Mutat 2001;18(4):264-281