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Interpretive Handbook

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Test 61820 :
Mucopolysaccharidosis IIIA, 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 IIIA (MPS-IIIA), or Sanfilippo syndrome A, is caused by mutations in the SGSH gene and is characterized by reduced or absent activity of the sulfamidase enzyme. This test screens for mutations in all 8 exons of the SGSH 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, accompanied by a rapid deterioration of social and adaptive skills. Death generally occurs by the 20s.

Useful For Suggests clinical disorders or settings where the test may be helpful

Identifying mutations within the SGSH gene

 

Confirmation of a diagnosis of mucopolysaccharidosis type IIIA

 

Carrier testing when there is a family history of mucopolysaccharidosis type IIIA, but disease-causing mutations have not been previously identified

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

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 MPS-IIIA 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-IIIA. The preferred approach to carrier testing is to first document the presence of an SGSH 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, Neijs S, Bruggenwirth HT, et al: Mucopolysaccharidosis type IIIA: clinical spectrum and genotype-phenotype correlations. Ann Neurol 2010;68(6):876-887

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


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