Sanfilippo syndrome: A mini-review

• Published in: Journal of inherited metabolic disease Vol. 31; no. 2; pp. 240 - 252
• Main Authors: Valstar, M. J., Ruijter, G. J. G., van Diggelen, O. P., Poorthuis, B. J., Wijburg, F. A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Dordrecht Springer Netherlands 01.04.2008; Springer; Blackwell Publishing Ltd
• Subjects: Acetylglucosaminidase - deficiency; Acetylglucosaminidase - genetics; Acetyltransferases - deficiency; Acetyltransferases - genetics; Adolescent; Adult; Animals; Biochemistry; Biological and medical sciences; Child; Child, Preschool; Genetic Predisposition to Disease; Heparitin Sulfate - metabolism; Human Genetics; Humans; Hydrolases - deficiency; Hydrolases - genetics; Incidence; Infant; Internal Medicine; Lysosomes - enzymology; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mucopolysaccharidosis III - diagnosis; Mucopolysaccharidosis III - enzymology; Mucopolysaccharidosis III - genetics; Mucopolysaccharidosis III - mortality; Mucopolysaccharidosis III - therapy; Pediatrics; Phenotype; Prognosis; SSIEM Symposium 2007; Sulfatases - deficiency; Sulfatases - genetics; Time Factors; Young Adult; Heparan Sulfate; Enzyme Replacement Therapy; Central Nervous System Pathology; Unrelated Cord Blood; Miglustat; Nutrition; Genetics; Metabolic diseases; Review; Bibliographic review; Syndrome; Genetic disease
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-008-0838-5

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.