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

Lenore S. Levine, Bo Dupont, Franziska Lorenzen, Songja Pang, Marilyn Pollack, Sharon Oberfield, Brenda Kohn, Alan Lerner, Emauele Cacciari, Franco Mantero, Alessandra Cassio, Carla Scaroni, Giuseppe Chiumello, Gian Filippo Rondanini, Luigi Gargantini, Giorgio Giovannelli, Raffaele Virdis, Edoardo Bartolotta, Cesare Migliori, Carlo PintorLuciano Tato, Francesco Barboni, Maria I. New

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


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 6 = 0.00 of 3.409. Close genetic linkage between HLA and 21-OHCRYPTIC w a g t h u g e s t a b l i s h e d 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.

Original languageEnglish
Pages (from-to)6-1324
Number of pages1319
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
StatePublished - Dec 1980
Externally publishedYes


Dive into the research topics of 'Cryptic 21-hydroxylase deficiency in families of patients with classical congenital adrenal hyperplasia'. Together they form a unique fingerprint.

Cite this