Sanfilippo types

Hopwood, J. J., and Elliott, H., Radiolabelled oligosaccharides as substrates for the estimation of sulfamidase and the detection of the. sanfilippo Type A syndrome. Clin. Chim. Acta 112, 55-66 (1981). 

He W, Voznyi YV, Boer AM, Kleijer WJ, van Diggelen OP (1993) A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type D (MPS HID). J Inherit Metab Dis 16 935-941... 

The Sanfilippo disease type A (MPS III) corrective factor is a heparan N-sulfatase. However, as is true for many other metabolic diseases, the same symptoms... 

Sanfllippo s syndrome (type III) This syndrome exhibits a similar clinical picture as described above with at least two different enzyme defects heparan-sulphamidase deficiency (type A) and N-acetyl-a-D-glucosamidase deficiency (type B) and possibly types C or D as well (S. X Sanfilippo et at, 1963). 

Stepwise degradation of heparan sulfate. The deficiency disea.ses corresponding to the numbered reactions are I = mucopolysaccharidosis (MPS) II, Hunter s syndrome 2 = MPS I, Hurler s, Scheie s, and Hurler-Scheie s syndromes 3 = MPS III A, Sanfilippo s syndrome type A 4 = MPS III C, Sanfilippo s syndrome type C 5 = MPS 111 B, Sanfilippo s syndrome type B 6 = no deficiency disease yet known 7 = MPS VII, Sly s syndrome 8 = MPS III D, Sanfilippo s syndrome type D. The schematic drawing depicts all structures known to occur within heparan sulfate and does not imply that they occur stoichiometrically. Very few of the glucuronic acid residues are sulfated. [Reproduced with permission from E. F. Neufeld and J. Muenzer. In Metabolic Basis of Inherited Disease, 7th ed., C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle (Eds). McGraw-Hill, New York, 1995, p. 2468.]... 

I Bcatyi transferase I HhooA Sanfilippo syndrome, Type C (MRS III C)... 

Sanfilippo s syndrome is an inherited genetic disorder of heparan sulfate catabolism, characterized by progressive mental retardation, mild skeletal deformities, and excretion of excessive amounts of heparan sulfate in the urine (Dorfman and Matalon, 1976 McKusick, 1972). A deficiency of heparan sulfiite N-sulfohydrolase is responsible for the pathogenesis of Sanfilippo s syndrome (type A) (Kresse and Neufeld, 1972 Kresse, 1973 Hop-wood and Elliott, 1981). The patients and heterozygotes are diagnosed by estimating heparan sulfate N-sulfohydrolase activity in fibroblasts and peripheral leukocytes (Schmidt et al., 1977). 

Schmidt, R., Von Figura, K., Paschke, E., and Kresse, H., Sanfilippo s disease type A Sul-famidase activity in peripheral leukocytes of normal, heterozygous and homozygous individuals. Clin. Chim. Acta 80, 7-15 (1977). 

The Sanfilippo syndrome, type A presents with severe and progressive mental retardation with sleep disturbances and behavioral problems as the most prominent features. The organ enlargement and joint stiffness seen in the other mucopolysaccharidoses is not present or occurs later in life. Diarrhea can be more severe and recurrent than in the other mucopolysaccharidoses. Onset of the disorder is usually between 1 and 6 years of age. Studies of the basic defect in Sanfilippo syndrome revealed that there are four separate disorders. The type of Sanfilippo syndrome is based on enzyme deficiency. The clinical symptoms in the four types overlap. The prevalence of Sanfilippo syndrome in the Netherlands is estimated at 1 in 24,000 for three of the four types [3]. However, using all four types of Sanfilippo syndrome, the study from Australia estimates the prevalence at 1 in 60,600, which is about 2.5 times lower than that in the Netherlands [2]. The Sanfilippo syndrome, type A, is estimated at 1 in 114,000 [2]. 

In the Sanfilippo syndrome, type B, severe and mild forms exist. The clinical features overlap for each with the type A disorder. Prevalence is estimated at 1 in 211,000 [2]. 

In the Sanfilippo syndrome, type D, the clinical features are more variable than any of the other types. The clinical features overlap for each of the Sanfilippo disorders. The urine of patients with Sanfilippo syndrome, type D, shows a variable increased excretion (or normal level) of the glycos-aminoglycan, heparan sulfate. The presence of heparan sulfate does not distinguish the type of Sanfilippo syndrome. Measurement of specific enzymes involved in the catabolism of heparan sulfate determines the type. 

Table 183. Heparin sulfaminidase (Sanfilippo syndrome, type A, MPS III A) ...

Table ISA N-Acetyl-a- -D-glucosaminidase (Sanfilippo syndrome, type B, MPS 1115) ...

Table 18.5 Acetyl CoA a-glucosaminidase N-acetyltransferase (Sanfilippo syndrome, type C, MPS IIIC) ...

Table 18.6. N-Acetylglucosamine 6-sulfatase Sanfilippo syndrome, type D, MPS HID)...

Sanfilippo syndrome, type C Sanfilippo syndrome, type D Santavuori disease Saposin B deficiency Sarcosine dehydrogenase deficiency Scheie syndrome Schindler disease Segawa disease... 

O Brien, J. S., Miller, A. L., Loverde, W. A., and Veath, M. L., 1973, Sanfilippo disease type B Enzyme replacement and metabolic correction in cultured fibroblasts. Science 181 753. 

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