Sanfilippo syndrome: A mini-review

Summary Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive disorder, caused by a deficiency in one of the four enzymes involved in the lysosomal degradation of the glycosaminoglycan heparan sulfate. Based on the enzyme deficiency, four different subtypes, MPS IIIA, B, C, and D, are recognized. The genes encoding these four enzymes have been characterized and various mutations have been reported. The probable diagnosis of all MPS III subtypes is based on increased concentration of heparan sulfate in the urine. Enzymatic assays in leukocytes and/or fibroblasts confirm the diagnosis and allow for discrimination between the different subtypes of the disease. The clinical course of MPS III can be divided into three phases. In the first phase, which usually starts between 1 and 4 years of age, a developmental delay becomes apparent after an initial normal development during the first 1–2 years of life. The second phase generally starts around 3–4 years and is characterized by severe behavioural problems and progressive mental deterioration ultimately leading to severe dementia. In the third and final stage, behavioural problems slowly disappear, but motor retardation with swallowing difficulties and spasticity emerge. Patients usually die at the end of the second or beginning of the third decade of life, although survival into the fourth decade has been reported. Although currently no effective therapy is yet available for MPS III, several promising developments raise hope that therapeutic interventions, halting the devastating mental and behavioural deterioration, might be feasible in the near future. Competing interests: None declared References to electronic databases: Mucopolysaccharidosis III: type A, OMIM #252900; type B, OMIM #252920; type C, OMIM #252930; type D, OMIM #252940. Heparan N-sulfatase: EC 3.10.1.1. N-Acetyl-α-glucosaminidase: EC 3.2.1.50. Acetyl-CoA:α-glucosaminide N-acetyltransferase: EC 2.3.1.78. N-Acetylglucosamine 6-sulfatase: EC 3.1.6.14. Presented at the Annual Symposium of the SSIEM, Hamburg, 4–7 September 2007.