Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene

• Published in: The journal of clinical endocrinology and metabolism Vol. 86; no. 11; pp. 5379 - 5382
• Main Authors: KAYES-WANDOVER, Kathleen M, TANNIN, Grace M, SHULMAN, Dorothy, PELED, Dror, JONES, Kenneth L, KARAVITI, Lefkothea, WHITE, Perrin C
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.11.2001
• Subjects: Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; Aldosterone - blood; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Cytochrome P-450 CYP11B2 - genetics; Endocrinopathies; Exons - genetics; Fludrocortisone - therapeutic use; Heterozygote; Humans; Hypoaldosteronism - blood; Hypoaldosteronism - drug therapy; Hypoaldosteronism - genetics; Introns - genetics; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oligonucleotides, Antisense; Renin - blood; Reverse Transcriptase Polymerase Chain Reaction; Endocrinopathy; Human; Adrenal cortex diseases; Congenital; Enzyme; Mineralocorticoid; Infant; Hyperreninemia; Hypoaldosteronism; Synthase; Aldosterone; Congenital disease; Genetic determinism; Case study; Adrenal insufficiency; Gene; Etiology; Adrenal gland diseases; Mutation
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.86.11.5379

Isolated hyperreninemic hypoaldosteronism presenting in infancy is usually caused by mutations in the CYP11B2 gene encoding aldosterone synthase. We studied five patients in four unrelated kindreds with hyperreninemic hypoaldosteronism, in whom we were unable to find such mutations. All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia. All responded to fludrocortisone treatment. There were no mutations detected in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in two unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least one of three polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage. These results demonstrate the existence of an inherited form of hyperreninemic hypoaldosteronism distinct from aldosterone synthase deficiency. The affected gene(s) remain to be determined.