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 or GAG). Undegraded or partially degraded GAG (also called mucopolysaccharides or MPS) are stored in lysosomes or are excreted in the urine. 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 is a MPS with 4 recognized types (A,B, C, and D) caused by different enzyme deficiencies; the clinical presentation of all types, however, is indistinguishable. Sanfilippo syndrome is characterized by severe central nervous system (CNS) degeneration, but other symptoms seen in MPS, such as coarse facial features, tend to be milder. Such disproportionate involvement of the CNS is unique among the MPS. 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, though individuals with an attenuated phenotype may have a longer life expectancy. Although there is no cure for Sanfilippo syndrome, research of therapies has included bone marrow transplantation, enzyme replacement, and gene replacement.
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 coding region and deletion/duplication studies are available for patients with an enzyme deficiency. Refer to www.genetests.org for a listing of laboratories currently offering this testing.
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
The preferred specimen type for diagnosing Sanfilippo syndrome type B is serum (ANAS / Alpha-N-Acetylglucosaminidase, Serum); however, if fibroblasts are readily available, ANAT / Alpha-N-Acetylglucosaminidase, Fibroblasts can also 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.
Interfering factors include lack of viable cells, bacterial contamination, failure to transport tissue in an appropriate media, excessive transport time, and exposure of the specimen to temperature extremes (freezing or >30 degrees C).
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.
> or =0.05 nmol/min/mg protein
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 Kindgom and Greece. Am J Med Genet A 2011;155A(1):58-68
2. Neufeld EF, Muenzer J: The mucopolysaccharidoses. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, D Valle, et al. New York, McGraw-Hill Book Company, 2001, pp 3421-3452
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