Journal of Inherited Metabolic Disease

, Volume 31, Issue 2, pp 240–252

Sanfilippo syndrome: A mini-review

  • M. J. Valstar
  • G. J. G. Ruijter
  • O. P. van Diggelen
  • B. J. Poorthuis
  • F. A. Wijburg
SSIEM Symposium 2007

DOI: 10.1007/s10545-008-0838-5

Cite this article as:
Valstar, M.J., Ruijter, G.J.G., van Diggelen, O.P. et al. J Inherit Metab Dis (2008) 31: 240. 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.

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

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • M. J. Valstar
    • 1
  • G. J. G. Ruijter
    • 2
  • O. P. van Diggelen
    • 2
  • B. J. Poorthuis
    • 3
  • F. A. Wijburg
    • 1
    • 4
  1. 1.Department of Pediatrics, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Clinical GeneticsErasmus University Medical CenterRotterdamThe Netherlands
  3. 3.Department of Medical Biochemistry, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  4. 4.Department of Pediatrics (G8-205)Academic Medical CenterAmsterdamThe Netherlands