Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1977 Apr;14(2):91–99. doi: 10.1136/jmg.14.2.91

Heterozygote detection in angiokeratoma corporis diffusum (Anderson-Fabry disease). Studies on plasma, leucocytes, and hair follicles.

M W Spence, A L Goldbloom, J K Burgess, D D'entremont, B A Ripley, K L Weldon
PMCID: PMC1013521  PMID: 404411

Abstract

Heterozygote detection for angiokeratoma corporis diffusum (Anderson-Fabry disease, ACD), an X-linked disorder of glycosphingolipid metabolism was examined using alpha-galactosidase activity, an alpha-galactosidase/beta-galactosidase activity ratios (alpha/beta ratio) in leucocytes, plasma, and hair follicles; For leucocytes, 22 obligate heterozygotes, 25 suspected heterozygotes, and 47 control subjects were studied, while for plasma, the groups were 17 obligate heterozygotes and 35 controls. The alpha/beta ratio in plasma and leucocytes was clearly a better discriminator between obligate heterozygotes and controls than alpha-galactosidase activity alone, but still failed to detect 3 obligates with leucocytes and 2 with plasma. Discrimination was not improved by joint use of plasma and leucocyte alpha/beta ratios, but was improved by measurement of hair-follicle alpha/beta ratios. The interdecile range of log (alpha-galactosidase/beta-galactosidase activity) in 20 hair follicles from each of 4 obligate and 7 suspected heterozygotes was clearly different from 11 control subjects. Accordingly, for rapid screening for carriers of ACD, we recommend use of leucocyte or plasma alpha/beta ratios which should detect greater than 85% of heterozygotes. When results are equivocal, and ancillary information suggests heterozygous status, the more time-consuming measurement of hair-follicle alpha/beta ratios is a useful additional test.

Full text

PDF
92

Selected References

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

  1. Avila J. L., Convit J., Velazquez-Avila G. Fabry's disease: normal alpha-galactosidase activity and urinary-sediment glycosphingolipid levels in two obligate heterozygotes. Br J Dermatol. 1973 Aug;89(2):149–157. doi: 10.1111/j.1365-2133.1973.tb02951.x. [DOI] [PubMed] [Google Scholar]
  2. Beutler E., Kuhl W. Biochemical and electrophoretic studies of -galactosidase in normal man, in patients with Fabry's disease, and in Equidae. Am J Hum Genet. 1972 May;24(3):237–249. [PMC free article] [PubMed] [Google Scholar]
  3. Brady R. O., Gal A. E., Bradley R. M., Martensson E., Warshaw A. L., Laster L. Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967 May 25;276(21):1163–1167. doi: 10.1056/NEJM196705252762101. [DOI] [PubMed] [Google Scholar]
  4. DAVIDSON R. G., NITOWSKY H. M., CHILDS B. DEMONSTRATION OF TWO POPULATIONS OF CELLS IN THE HUMAN FEMALE HETEROZYGOUS FOR GLUCOSE-6-PHOSPHATE DEHYDROGENASE VARIANTS. Proc Natl Acad Sci U S A. 1963 Sep;50:481–485. doi: 10.1073/pnas.50.3.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Danes B. S., Bearn A. G. Hurler's syndrome: a genetic study of clones in cell culture with particular reference to the Lyon hypothesis. J Exp Med. 1967 Sep 1;126(3):509–522. doi: 10.1084/jem.126.3.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Del Monte M. A., Johnson D. L., Cotlier E., Krivit W., Desnick R. J. Letter: Diagnosis of Fabry's disease by tear alpha-galactosidase A. N Engl J Med. 1974 Jan 3;290(1):57–58. doi: 10.1056/NEJM197401032900118. [DOI] [PubMed] [Google Scholar]
  7. Desnick R. J., Allen K. Y., Desnick S. J., Raman M. K., Bernlohr R. W., Krivit W. Fabry's disease: enzymatic diagnosis of hemizygotes and heterozygotes. Alpha-galactosidase activities in plasma, serum, urine, and leukocytes. J Lab Clin Med. 1973 Feb;81(2):157–171. [PubMed] [Google Scholar]
  8. Francke U., Bakay B., Nyhan W. L. Detection of heterozygous carriers of the Lesch-Nyhan syndrome by electrophoresis of hair root lysates. J Pediatr. 1973 Mar;82(3):472–478. doi: 10.1016/s0022-3476(73)80123-4. [DOI] [PubMed] [Google Scholar]
  9. Gartler S. M., Gandini E., Angioni G., Argiolas N. Glucose-6 phosphate dehydrogenase mosaicism: utilization as a tracer in the study of the development of hair root cells. Ann Hum Genet. 1969 Oct;33(2):171–176. doi: 10.1111/j.1469-1809.1969.tb01642.x. [DOI] [PubMed] [Google Scholar]
  10. Gartler S. M., Gansini E., Hutchison H. T., Campbell B., Zechhi G. Glucose-6-phosphate dehydrogenase mosaicism: ito;ozatopm om tje study of hair follicle variegation. Ann Hum Genet. 1971 Jul;35(1):1–7. [PubMed] [Google Scholar]
  11. Gartler S. M., Scott R. C., Goldstein J. L., Campbell B. Lesch-Nyhan syndrome: rapid detection of heterozygotes by use of hair follicles. Science. 1971 May 7;172(3983):572–574. doi: 10.1126/science.172.3983.572. [DOI] [PubMed] [Google Scholar]
  12. Ho M. W., Beutler S., Tennant L., O'Brien J. S. Fabry's disease: evidence for a physically altered -galactosidase. Am J Hum Genet. 1972 May;24(3):256–266. [PMC free article] [PubMed] [Google Scholar]
  13. Kattamis C. A. Glucose-6-phosphate dehydrogenase deficiency in female heterozygotes and the X-inactivation hypothesis. Acta Paediatr Scand. 1967;(Suppl):103+–103+. doi: 10.1111/j.1651-2227.1967.tb15284.x. [DOI] [PubMed] [Google Scholar]
  14. Kint J. A. Fabry's disease: alpha-galactosidase deficiency. Science. 1970 Feb 27;167(3922):1268–1269. doi: 10.1126/science.167.3922.1268. [DOI] [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. LYON M. F. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 1961 Apr 22;190:372–373. doi: 10.1038/190372a0. [DOI] [PubMed] [Google Scholar]
  17. Mapes C. A., Anderson R. L., Sweeley C. C. Galactosylgalactosylglucosylceramide: Galactosyl hydrolase in normal human plasma and its absence in patients with fabry's disease. FEBS Lett. 1970 Apr 2;7(2):180–182. doi: 10.1016/0014-5793(70)80151-x. [DOI] [PubMed] [Google Scholar]
  18. Mapes C. A., Sweeley C. C. Galactosyl (alpha 1--4)galactosylceramide: galactosyl hydrolase activity in normal and Fabry plasma. Biochem Biophys Res Commun. 1973 Aug 21;53(4):1317–1324. doi: 10.1016/0006-291x(73)90609-8. [DOI] [PubMed] [Google Scholar]
  19. Mapes C. A., Sweeley C. C. Preparation and properties of an affinity column adsorbent for differentiation of multiple forms of -galactosidase activity. J Biol Chem. 1973 Apr 10;248(7):2461–2470. [PubMed] [Google Scholar]
  20. Mapes C. A., Sweeley C. C. Substrate specificity of ceramide trihexosidase. FEBS Lett. 1972 Sep 15;25(2):279–281. doi: 10.1016/0014-5793(72)80503-9. [DOI] [PubMed] [Google Scholar]
  21. McKnight M. T., Spence M. W. Attempted detection of heterozygotes for maple-syrup-urine disease. Clin Genet. 1972;3(6):458–464. doi: 10.1111/j.1399-0004.1972.tb01481.x. [DOI] [PubMed] [Google Scholar]
  22. Migeon B. R., Der Kaloustian V. M., Nyhan W. L., Yough W. J., Childs B. X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: heterozygote has two clonal populations. Science. 1968 Apr 26;160(3826):425–427. doi: 10.1126/science.160.3826.425. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Philippart M., Sarlieve L., Manacorda A. Urinary glycolipids in Fabry's disease. Their examination in the detection of atypical variants and the pre-symptomatic state. Pediatrics. 1969 Feb;43(2):201–206. [PubMed] [Google Scholar]
  25. Rietra P. J., Tager J. M., de Groot W. P. Detection of Fabry hemizygotes and heterozygotes by measurement of -galactosidase in urine. Clin Chim Acta. 1972 Aug;40(1):229–235. doi: 10.1016/0009-8981(72)90275-6. [DOI] [PubMed] [Google Scholar]
  26. Romeo G., Migeon B. R. Genetic inactivation of the alpha-galactosidase locus in carriers of Fabry's disease. Science. 1970 Oct 9;170(3954):180–181. doi: 10.1126/science.170.3954.180. [DOI] [PubMed] [Google Scholar]
  27. Silvers D. N., Cox R. P., Balis M. E., Dancis J. Detection of heterozygote in Lesch-Nyhan disease by hair-root analysis. N Engl J Med. 1972 Feb 24;286(8):390–395. doi: 10.1056/NEJM197202242860802. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Stamatoyannopoulos G., Papayannopoulou T., Bakopoulos C., Motulsky A. G. Detection of glucose-6-phosphate dehydrogenase deficient heterozygotes. Blood. 1967 Jan;29(1):87–101. [PubMed] [Google Scholar]
  30. Wood S., Nadler H. L. Fabry's disease: absence of an -galactosidase isozyme. Am J Hum Genet. 1972 May;24(3):250–255. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES