Journal of Clinical Endocrinology & Metabolism, Vol 51, 1316-1324, Copyright © 1980 by Endocrine Society

ARTICLES

Cryptic 21-hydroxylase deficiency in families of patients with classical congenital adrenal hyperplasia

LS Levine, B Dupont, F Lorenzen, S Pang, M Pollack, S Oberfield, B Kohn, A Lerner, E Cacciari, F Mantero, A Cassio, C Scaroni, G Chiumello, GF Rondanini, L Gargantini, G Giovannelli, R Virdis, E Bartolotta, C Migliori, C Pintor, L Tato, F Barboni and MI New

Serum androgens and 17-hydroxyprogesterone concentrations and HLA genotypes were determined in 124 families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). In 8 pedigrees, we discovered 16 pubertal or postpubertal family members of either sex who had biochemical evidence of 21-hydroxylase deficiency but were without clinical symptoms of excess virilism, amenorrhea, or infertility. We designated these family members as individuals with cryptic 21-hydroxylase deficiency. Within each generation, the family members with cryptic 21-hydroxylase deficiency were HLA identical. It is proposed that these family members are genetic compounds, having 21- hydroxylase deficiency as a result of two recessive gene defects: 1) a severe 21-hydroxylase gene defect present in the index case with classical CAH (21-OHCAH) and 2) a mild 21-hydroxylase gene defect (21- OHCRYPTIC). Thus, the CAH genotype in the family members with cryptic 21-hydroxylase deficiency is 21-OHCAH/21-OHCRYPTIC. Lod score analysis for linkage between the cryptogenic 21-OH trait and HLA gave a combined Lod score for males and females of theta = 0.00 of 3.409. Close genetic linkage between HLA and 21-OHCRYPTIC was thus established. This study provides support for the previously reported heterogeneity of 21- hydroxylase deficiency which may result from allelic variability at the locus for steroid 21-hydroxylase.

This article has been cited by other articles:

				R. S. Araujo, B. B. Mendonca, A. S. Barbosa, C. J. Lin, J. A. M. Marcondes, A. E. C. Billerbeck, and T. A. S. S. Bachega Microconversion between CYP21A2 and CYP21A1P Promoter Regions Causes the Nonclassical Form of 21-Hydroxylase Deficiency J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 4028 - 4034. [Abstract] [Full Text] [PDF]

				M. I. New Nonclassical 21-Hydroxylase Deficiency J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4205 - 4214. [Abstract] [Full Text] [PDF]

				M. I. NEW An Update of Congenital Adrenal Hyperplasia Ann. N.Y. Acad. Sci., December 1, 2004; 1038(1): 14 - 43. [Abstract] [Full Text] [PDF]

				M. I. New and R. C. Wilson Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess PNAS, October 26, 1999; 96(22): 12790 - 12797. [Abstract] [Full Text] [PDF]