Prenatal diagnosis of Sanfilippo disease type B

Abstract

The prenatal diagnosis of a fetus affected with Sanfilippo disease type B is described. The deficiency of alpha-N-acetylglucosaminidase in the cultured amniotic fluid cells was shown by a microassay enabling early prenatal diagnosis. In addition an increased level of heparan sulphate was demonstrated in the amniotic fluid by two-dimensional electrophoresis of glycosaminoglycans. The latter result confirmed the value of this test as an adjunctive method in the prenatal diagnosis. The pregnancy was terminated and the prenatal diagnosis was confirmed by enzyme analysis of cultured fetal fibroblasts and fetal liver.

Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes

“…The low frequency of individual mutations makes it unlikely that mutation screening will improve the accuracy of the initial diagnostic procedures based on the analysis of metabolites and the determination of enzyme activity, the latter being sensitive enough for prenatal diagnosis. 25,26 However, mutation analysis will allow carrier-testing for siblings, especially if a partner is consanguineous, and will enable a more accurate prognosis for families of newly diagnosed patients, thereby improving genetic counselling. Mutation analysis is also of great importance for the selection of patients for trials of enzyme or gene replacement therapies and the evaluation of the efficacy of the protocols.…”

Prenatal Diagnosis of Sanfilippo a Syndrome: Experience in 35 Pregnancies at Risk and the Use of a New Fluorogenic Substrate for the Heparin Sulphamidase Assay

“…Simultaneous CVS and early amniocentesis would combine the advantages of having two supplementary methods and an early diagnosis, but the occasional and unforeseen need to back up the results on CV may not justify routine application of a double sampling procedure. Amniocentesis (at 16 weeks) will, however, be the method of choice if the specific type of Sanfilippo disease in the previous affected child has not been demonstrated by enzyme assay as GAG electrophoresis will probably detect all four types (shown for A,B and C; this report; Kleijer et al, 1984, Wang He et al, 1994 and even other MPS types.…”

“…Two-dimensional electrophoresis of GAGS in cell-free AF samples was performed as described elsewhere (Abeling et al, 1974;Mossman and Patrick, 1982;Kleijer et al, 1984).…”

“…CCC 0197-385 1/96/09082947 Prenatal diagnosis may be performed in the first trimester by chorionic villus sampling (CVS) and direct enzyme analysis of the villi (Kleijer et al, 1986) or by amniocentesis, which allows two tests to be done, i.e., the demonstration of heparan sulphate in the fluid by two-dimensional electrophoresis of glycosaminoglycans (GAGS) (Mossman and Patrick, 1982) or by enzyme assay in the cultured amniocytes (Harper et al, 1974). In the past, [35S]-sulphate uptake study in cultured amniocytes has been a useful adjunctive test in the prenatal diagnosis of most types of MPS (e.g., for MPS I: Kleijer et al, 1983) but this method provides relatively late results and in the case of Sanfilippo syndrome, only moderate intracellular accumulation of GAGS is found (Kleijer et al, 1984).…”

A clinical biochemist's view of the investigation of suspected inherited metabolic disease

“…With slight modifications, the two-dimensional electrophoresis can be used for prenatal diagnosis of mucopolysaccharidosis, which we described in 1984 (Kleijer et al, 1984b). Figures 11 and 12 are examples of abnormal electrophoretic pictures in amniotic fluid.…”