Abstract
4-Methylumbelliferyl derivatives of β-N-acetylglucosamine-6-sulfate and β-N-acetylgalactosamine-6-sulfate were prepared by direct sulfation of the commonly used unsulfated derivatives. Both sulfated substrates were highly specific for hexosaminidase (Hex) A and in fractionated samples more than 97% of these activities was found in the Hex A fraction. The thermolability of Hex B and intermediate forms as found in subjects with hereditary heatlabile Hex B, and the increase in an intermediate Hex form as found in serum during pregnancy (Hex P), had no effect on direct determination of Hex A with the sulfated fluorogenic substrates. Serum and leukocytes from patients with infantile Tay-Sachs disease (TSD), including a TSD patient with heatlabile Hex B, had less than 2% of the respective mean activity of non-carriers. The latter patient was estimated to have 24% Hex A based on the heat inactivation method. Carrier values in serum during pregnancy and in samples with heatlabile Hex B were within the range of other carrier values and clearly separated from the respective non-carrier values. Mean carrier activities were 51-56% of the respective non-carrier means. The values of % Hex A as derived from the ratio between activities toward sulfated and unsulfated substrates were comparable to those obtained by heat inactivation excluding those with heatlabile Hex B. This helps detecting TSD genotypes and discriminates them from Sandhoff disease genotypes.
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Ben-Yoseph, Y., Reld, J. & Nadler, H. 801 DIAGNOSIS AND CARRIER DETECTION OF TAY-SACHS DISEASE USING SULFATED FLUOROGENIC SUBSTRATES: DIRECT DETERMINATION OF HEXOSAMINIDASE A IN SERUM DURING PREGNANCY AND IN THE PRESENCE OF HEREDITARY HEATLABILE HEXOSAMINIDASE B. Pediatr Res 19, 244 (1985). https://doi.org/10.1203/00006450-198504000-00831
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DOI: https://doi.org/10.1203/00006450-198504000-00831