Mucopolysaccharidosis IIIB, Full Gene Analysis
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.
Identifying mutations within the NAGLU gene
Confirmation of a diagnosis of mucopolysaccharidosis type IIIB
Carrier testing when there is a family history of mucopolysaccharidosis type IIIB, but disease-causing mutations have not 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
A small percentage of individuals who are carriers or have a diagnosis of mucopolysaccharidosis type IIIB (MPS-IIIB) may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of MPS-IIIB. The preferred approach to carrier testing is to first document the presence of an NAGLU gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
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.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
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