Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1985 Sep;37(5):912–921.

Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. I. Statistical methods.

R M Cantor, J S Lim, C Roy, M M Kaback
PMCID: PMC1684685  PMID: 4050790

Abstract

Serum and leukocyte hexosaminidase profiles (total activity and percent heat-labile activity levels) in obligate Sandhoff disease (SHD) heterozygotes differ from those of obligate Tay-Sachs disease (TSD) heterozygotes and noncarrier individuals. We have developed a procedure to identify, with 95% sensitivity, carriers of the allele(s) for SHD among individuals screened in a TSD heterozygote identification program. Using multivariate statistical methods of cluster analysis and discriminant analysis on serum and leukocyte hexosaminidase profiles from 102 potential SHD carriers, a linear discriminant function to classify individuals as SHD carriers or SHD noncarriers was constructed. This function classifies the serum and leukocyte profiles from all 15 obligate SHD heterozygotes studied, as those of SHD carriers. A 95% isodensity ellipse derived from only the serum hexosaminidase profiles of the 15 SHD obligate carriers has been applied to a TSD screened sample of 37,843 Jewish and non-Jewish individuals. A potential recall rate of screened individuals for serum retests and leukocyte assays of 2.01% has been estimated. These statistical methods enhance the TSD heterozygote screening program by permitting one to detect SHD heterozygotes within the screened population.

Full text

PDF
912

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Der Kaloustian V. M., Khoury M. J., Hallal R., Idriss Z. H., Deeb M. E., Wakid N. W., Haddad F. S. Sandhoff disease: a prevalent form of infantile GM2 gangliosidosis in Lebanon. Am J Hum Genet. 1981 Jan;33(1):85–89. [PMC free article] [PubMed] [Google Scholar]
  2. Gilbert F., Kucherlapati R., Creagan R. P., Murnane M. J., Darlington G. J., Ruddle F. H. Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes. Proc Natl Acad Sci U S A. 1975 Jan;72(1):263–267. doi: 10.1073/pnas.72.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gold R. J., Maag U. R., Neal J. L., Scriver C. R. The use of biochemical data in screening for mutant alleles and in genetic counselling. Ann Hum Genet. 1974 Jan;37(3):315–326. doi: 10.1111/j.1469-1809.1974.tb01838.x. [DOI] [PubMed] [Google Scholar]
  4. Kaback M. M., Bailin G., Hirsch P., Roy C. Automated thermal fractionation of serum hexosaminidase: effects of alteration in reaction variables and implications for Tay-Sachs disease heterozygote screening. Prog Clin Biol Res. 1977;18:197–212. [PubMed] [Google Scholar]
  5. Lachenbruch P. A. An almost unbiased method of obtaining confidence intervals for the probability of misclassification in discriminant analysis. Biometrics. 1967 Dec;23(4):639–645. [PubMed] [Google Scholar]
  6. Lane A. B., Young E., Jenkins T. Segregation of Tay-Sachs and Sandhoff alleles in a non-Jewish family. Am J Hum Genet. 1980 Nov;32(6):920–926. [PMC free article] [PubMed] [Google Scholar]
  7. Lowden J. A., Ives E. J., Keene D. L., Burton A. L., Skomorowski M. A., Howard F. Carrier detection in Sandhoff disease. Am J Hum Genet. 1978 Jan;30(1):38–45. [PMC free article] [PubMed] [Google Scholar]
  8. Molzer B., Bernheimer H. Detection of GM2-gangliosidosis (Tay-Sachs and Sandhoff disease) gene carriers by serum hexosaminidase assay. Clin Chim Acta. 1976 Nov 15;73(1):163–169. doi: 10.1016/0009-8981(76)90318-1. [DOI] [PubMed] [Google Scholar]
  9. O'Brien J. S., Okada S., Chen A., Fillerup D. L. Tay-sachs disease. Detection of heterozygotes and homozygotes by serum hexosaminidase assay. N Engl J Med. 1970 Jul 2;283(1):15–20. doi: 10.1056/NEJM197007022830104. [DOI] [PubMed] [Google Scholar]
  10. O'Brien J. S., Okada S., Fillerup D. L., Veath M. L., Adornato B., Brenner P. H., Leroy J. G. Tay-Sachs disease: prenatal diagnosis. Science. 1971 Apr 2;172(3978):61–64. doi: 10.1126/science.172.3978.61. [DOI] [PubMed] [Google Scholar]
  11. Sandhoff K., Andreae U., Jatzkewitz H. Deficient hexozaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs. Life Sci. 1968 Mar 15;7(6):283–288. doi: 10.1016/0024-3205(68)90024-6. [DOI] [PubMed] [Google Scholar]
  12. Schneck L., Valenti C., Amsterdam D., Friedland J., Adachi M., Volk B. W. Prenatal diagnosis of Tay-Sachs disease. Lancet. 1970 Mar 21;1(7647):582–584. doi: 10.1016/s0140-6736(70)91624-7. [DOI] [PubMed] [Google Scholar]
  13. Spence M. W., Ripley B. A., Embil J. A., Tibbles J. A. A new variant of Sandhoff's disease. Pediatr Res. 1974 Jun;8(6):628–637. doi: 10.1203/00006450-197406000-00003. [DOI] [PubMed] [Google Scholar]
  14. Suzuki Y., Koizumi Y., Togari H., Ogawa Y. Sandhoff disease: diagnosis of heterozygous carriers by serum hexosaminidase assay. Clin Chim Acta. 1973 Oct 12;48(2):153–158. doi: 10.1016/0009-8981(73)90360-4. [DOI] [PubMed] [Google Scholar]
  15. Varki A., Reitman M. L., Vannier A., Kornfeld S., Grubb J. H., Sly W. S. Demonstration of the heterozygous state for I-cell disease and pseudo-Hurler polydystrophy by assay of N-acetylglucosaminylphosphotransferase in white blood cells and fibroblasts. Am J Hum Genet. 1982 Sep;34(5):717–729. [PMC free article] [PubMed] [Google Scholar]
  16. Warner T. G., O'Brien J. S. Genetic defects in glycoprotein metabolism. Annu Rev Genet. 1983;17:395–441. doi: 10.1146/annurev.ge.17.120183.002143. [DOI] [PubMed] [Google Scholar]
  17. Wood S., MacDougall B. G. Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts. Am J Hum Genet. 1976 Sep;28(5):489–495. [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES