Sanfilippo syndrome: a mini-review

Topic: Brain proteins, microglia and lab models

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.

Key findings

• 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.

Why it matters

This review describes Sanfilippo syndrome, a rare inherited disorder in which a buildup of heparan sulfate leads to progressive mental deterioration and severe dementia, with patients usually dying in the second or third decade of life. It is about a different, rare disease and does not address treating, curing, or preventing Alzheimer's disease.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1007/s10545-008-0838-5
• PubMed: 18392742
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{valstar2008-18392742,
  author  = {Valstar, M. J. and Ruijter, G. J. and van Diggelen, O. P. and Poorthuis, B. J. and Wijburg, F. A.},
  title   = {{Sanfilippo syndrome: a mini-review}},
  journal = {Journal of inherited metabolic disease},
  year    = {2008},
  doi     = {10.1007/s10545-008-0838-5},
  pmid    = {18392742},
  url     = {https://doi.org/10.1007/s10545-008-0838-5}
}

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