Mucopolysaccharidosis type IIID (MPS IIID, Sanfilippo syndrome type D) is a member of a group of inherited metabolic disorders collectively termed mucopolysaccharidoses (MPSs). The MPSs are caused by a deficiency of lysosomal enzymes required for the degradation of mucopolysaccharides or glycosaminoglycans (GAGs) within the lysosome. When functioning normally, the lysosomal enzymes break down these GAGs, however when the enzyme is deficient, the GAGs build up in the lysosomes causing damage to the bodys tissues. The MPSs share a chronic progressive course with multisystem involvement, characteristic physical features, laboratory findings, and radiographic abnormalities.
MPS IIID is an autosomal recessive disorder caused by a deficiency of the N-acetylglucosamine 6-sulfatase (GNS) enzyme and build up of heparin sulfate. Clinical features of MPS IIID include hyperactivity, aggressiveness, and developmental delays. Mental abilities decline as the disease progresses. Involvement of other organ systems tends to be mild and dysmorphic features are subtle than those observed in other types of mucopolysaccharidosis . MPS IIID is caused by mutations in the GNS gene, but the disorder is clinically indistinguishable from MPS IIIA, MPS IIIB, and MPS IIIC, which are caused by mutations in other genes. All four forms of MPS III result in buildup of the same GAG, heparin sulfate. Diagnostic sequencing analysis of the GNS gene coding region is available for MPS type IIID patients and their at-risk relatives on a clinical basis.
For questions about testing for MPS IIID, call EGL Genetics at 470-378-2200. For further clinical information about lysosomal storage diseases, including management and treatment, call the Emory Lysosomal Storage Disease Center at (404) 778-8565 or (800) 200-1524.
1). Muenzer, J., The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr, 2004. 144(5 Suppl): p. S27-34.
2). Beesley, C.E., D. Burke, M. Jackson, A. Vellodi, B.G. Winchester, and E.P. Young, Sanfilippo syndrome type D: identification of the first mutation in the N-acetylglucosamine-6-sulphatase gene. J Med Genet, 2003. 40(3): p. 192-4.
3). Beesley, C.E., D. Concolino, M. Filocamo, B.G. Winchester, and P. Strisciuglio, Identification and characterisation of an 8.7kb deletion and a novel nonsense mutation in two Italian families with Sanfilippo syndrome type D (mucopolysaccharidosis IIID). Mol Genet Metab, 2006.
4). Mok, A., H. Cao, and R.A. Hegele, Genomic basis of mucopolysaccharidosis type IIID (MIM 252940) revealed by sequencing of GNS encoding N-acetylglucosamine-6-sulfatase. Genomics, 2003. 81(1): p. 1-5
- Confirmation of a clinical diagnosis of MPS IIID
- Prenatal testing for known familial mutations.
- Assessment of carrier status in high risk family members known mutation analysis.
DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.
Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must interpreted in the context of the patient's clinical and/or biochemical phenotype.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
- Mucopolysaccharide screen (urine GAG) (GA)
- Gene Sequencing for MPS IIIA (AW) and MPS IIIB (BB)
- Known mutation analysis (Custom Diagnostics) is available to test family members.
- Prenatal testing is available for known familial mutations only. Please call the Laboratory Genetic Counselor for specific requirements for prenatal testing before collecting a fetal sample.