Abstract
Serum hexosaminidase A (hex A) activity is reduced in obligate carriers of the TSD gene. The heat lability of hex A when exposed to 50-52°C under standard conditions has been employed for carrier detection in mass screening programs. Our experience with a program involving tests on more than 3,500 persons has revealed more than 50% false positives on retesting by independent and more sensitive methods. Moreover, thermal lability tests of serum ‘rom obligate heterozygotes have shown at least a 15% overlap with normals. Assay of leukocyte hex A also lacks sufficient precision because hex B in white cell extracts is significantly less heat stable than in serum. Application of DEAE ion exchange chromatography for separation and quantitation of hex A yields better discrimination of heterozygotes from noncarriers (noncarrier 10.0 ± 1.22; obligate heterozygotes 4. 6 ± 1.20; newly identified carriers 5.1 ± 0.95 in nM/ml/min). A large “I” component can be separated from serum and tissues from TSD patients, and intermediate levels are observed in carriers. The “I” fraction is indistinguishable from hex B by kinetic or thermal stability properties, and resembles the “P” fraction observed during pregnancy. Our studies suggest that hex A deficiency in TSD may reflect an abnormality in “enzyme realization” - i.e. conversion of hex A from a precursor protein.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nitowsky, H., Nakagawa, S. & Kumin, S. PITFALLS IN DIFFERENTIAL HEAT INACTIVATION OF HEXOSAMJNIDASE FOR HETEROZYGOTE DETECTION FOR TAY-SACHS DISEASE (TSD). Pediatr Res 8, 437 (1974). https://doi.org/10.1203/00006450-197404000-00582
Issue Date:
DOI: https://doi.org/10.1203/00006450-197404000-00582