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Sanfilippo syndrome: A mini-review

  • SSIEM Symposium 2007
  • Published:
Journal of Inherited Metabolic Disease

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.

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Abbreviations

AAV:

adeno-associated virus

ASSC:

active-site-specific chaperone

CNS:

central nervous system

CSF:

cerebral spinal fluid

CVS:

chorionic villus samples

DMB:

dimethylmethylene blue

EET:

enzyme enhancement therapy

EGF:

epidermal growth factor

ENT:

ear, nose, throat

ER:

endoplasmatic reticulum

ERT:

enzyme replacement therapy

GAG:

glycosaminoglycan

GNS:

N-acetylglucosamine 6-sulfatase

HCT:

haematopoietic cell transplantation

HGSNAT:

acetyl-CoA:α-glucosaminide N-acetyltransferase

HS:

heparan sulfate

LSD:

lysosomal storage disorder

M6P:

mannose-6-phosphate

MPS:

mucopolysaccharidosis

NAGLU:

N-acetyl-α-glucosaminidase

P-GUS:

phosphorylated β-glucuronidase

Rh B:

rhodamine B

SDT:

substrate deprivation therapy

SGSH:

heparan N-sulfatase

SUMF1:

sulfatase modifying factor 1

UCB:

unrelated cord blood

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Authors and Affiliations

  1. Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    M. J. Valstar & F. A. Wijburg

  2. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands

    G. J. G. Ruijter & O. P. van Diggelen

  3. Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    B. J. Poorthuis

  4. Department of Pediatrics (G8-205), Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    F. A. Wijburg

Authors
  1. M. J. Valstar
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  2. G. J. G. Ruijter
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  3. O. P. van Diggelen
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  4. B. J. Poorthuis
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  5. F. A. Wijburg
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Corresponding author

Correspondence to F. A. Wijburg.

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Communicating editor: Ed Wraith

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.

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Valstar, M.J., Ruijter, G.J.G., van Diggelen, O.P. et al. Sanfilippo syndrome: A mini-review. J Inherit Metab Dis 31, 240–252 (2008). https://doi.org/10.1007/s10545-008-0838-5

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  • DOI: https://doi.org/10.1007/s10545-008-0838-5

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