Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome type A), 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 body's tissues. The MPSs share a chronic progressive course with multisystem involvement, characteristic physical features, laboratory findings, and radiographic abnormalities. MPS IIIA is an autosomal recessive condition caused by a deficiency of the enzyme heparan N-sulfatase.
Clinical features of MPS IIIA include hyperactivity, aggressiveness, and developmental delays in childhood. 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 type of mucopolysaccharidosis .
MPS IIIA is caused by mutations in the SGSH gene, but is clinically indistinguishable from MPS IIIB, MPS IIIC, and MPS IIID, 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 SGSH gene coding region is available for MPS type IIIA 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., E.P. Young, A. Vellodi, and B.G. Winchester, Mutational analysis of Sanfilippo syndrome type A (MPS IIIA): identification of 13 novel mutations. J Med Genet, 2000. 37(9): p. 704-7.
3). Lee-Chen, G.J., S.P. Lin, M.H. Ko, C.K. Chuang, C.P. Chen, H.H. Lee, S.C. Cheng, C.H. Shen, K.L. Tseng, and C.L. Li, Identification and characterization of mutations underlying Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA). Clin Genet, 2002. 61(3): p. 192-7.
- Confirmation of a clinical diagnosis of MPS IIIA.
- 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.
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.
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
- Mucopolysaccharide screen (urine GAG) (GA)
- Gene sequencing for MPS IIIB (BB) and MPS IIID (BH)
- 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.