Prenatal diagnosis of congenital lipoid adrenal hyperplasia

Paul Saenger, Zoi Klonari, Adiel Fleischer, Cyril A.L. Abram, Nathalie Compagnone, Synthia H. Mellon, Stephen M. Black, Walter L. Miller, Cedric H.L. Shackelton

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Abstract

Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare genetic disorder of adrenal and gonadal steroidogenesis of unknown cause in which cholesterol cannot be converted to pregnenolone. As a result, affected individuals can make no steroid hormones, so that all affected newborns are phenotypic females, irrespective of karyotype. We studied two pregnancies in a family with two previously affected children by examining fetal karyotype, genital ultrasonography, and amniotic fluid steroid concentrations and by performing ACTH tests on family members. Prenatal diagnosis correctly identified both an unaffected XX fetus and an affected XY fetus. In the affected pregnancy, amniotic fluid concentrations of progesterone and pregnenolone were 30% and 50% of normal, respectively, but concentrations of 17 alpha-hydroxypregnenolone, 17 α-hydroxyprogesterone, cortisol, dehydroepiandrosterone, androstenedione, and estriol were either extremely low or undetectable, suggesting that these detected steroids were donated by maternal steroidogenesis. Fetal cord blood obtained at the termination of pregnancy showed very low concentrations of estrogens donated by the mother’s circulation. Absent fetal steroidogenesis was confirmed by gas chromatography and mass spectrometry of both fetal and maternal serum. The responses of 10 different steroids to adrenal stimulation with ACTH in the obligately heterozygous parents were normal. Thus, unlike the case with other forms of CAH, heterozygosity cannot be determined by hormonal responses to provocative testing with ACTH. Immunocytochemistry and Western blotting showed that the affected placental tissue contained P450scc protein, confirming that P450scc is intact in these patients.

Original languageEnglish (US)
Pages (from-to)200-205
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number1
DOIs
StatePublished - Jan 1 1995

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Prenatal Diagnosis
Adrenocorticotropic Hormone
Pregnenolone
Steroids
Mothers
Amniotic Fluid
17-alpha-Hydroxypregnenolone
Steroid hormones
Fetal Blood
Karyotype
Pregnancy
17-alpha-Hydroxyprogesterone
Ultrasonography
Estriol
Fetus
Fluids
Dehydroepiandrosterone
Androstenedione
Gas chromatography
Inborn Genetic Diseases

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Saenger, P., Klonari, Z., Fleischer, A., Abram, C. A. L., Compagnone, N., Mellon, S. H., ... Shackelton, C. H. L. (1995). Prenatal diagnosis of congenital lipoid adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism, 80(1), 200-205. https://doi.org/10.1210/jcem.80.1.7829612

Prenatal diagnosis of congenital lipoid adrenal hyperplasia. / Saenger, Paul; Klonari, Zoi; Fleischer, Adiel; Abram, Cyril A.L.; Compagnone, Nathalie; Mellon, Synthia H.; Black, Stephen M.; Miller, Walter L.; Shackelton, Cedric H.L.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 1, 01.01.1995, p. 200-205.

Research output: Contribution to journalArticle

Saenger, P, Klonari, Z, Fleischer, A, Abram, CAL, Compagnone, N, Mellon, SH, Black, SM, Miller, WL & Shackelton, CHL 1995, 'Prenatal diagnosis of congenital lipoid adrenal hyperplasia', Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 1, pp. 200-205. https://doi.org/10.1210/jcem.80.1.7829612
Saenger P, Klonari Z, Fleischer A, Abram CAL, Compagnone N, Mellon SH et al. Prenatal diagnosis of congenital lipoid adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism. 1995 Jan 1;80(1):200-205. https://doi.org/10.1210/jcem.80.1.7829612
Saenger, Paul ; Klonari, Zoi ; Fleischer, Adiel ; Abram, Cyril A.L. ; Compagnone, Nathalie ; Mellon, Synthia H. ; Black, Stephen M. ; Miller, Walter L. ; Shackelton, Cedric H.L. / Prenatal diagnosis of congenital lipoid adrenal hyperplasia. In: Journal of Clinical Endocrinology and Metabolism. 1995 ; Vol. 80, No. 1. pp. 200-205.
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