Corticosterone methyloxidase deficiency, also known as aldosterone synthase deficiency, is a disorder characterized by excessive amounts of sodium released in the urine (salt wasting), along with insufficient release of potassium in the urine, usually beginning in the first few weeks of life. This imbalance leads to low levels of sodium and high levels of potassium in the blood (hyponatremia and hyperkalemia, respectively). Individuals with corticosterone methyloxidase deficiency can also have high levels of acid in the blood (metabolic acidosis).

The hyponatremia, hyperkalemia, and metabolic acidosis associated with corticosterone methyloxidase deficiency can cause nausea, vomiting, dehydration, low blood pressure, extreme tiredness (fatigue), and muscle weakness. Affected infants often experience failure to thrive, which means they do not gain weight and grow at the expected rate. Severe cases of corticosterone methyloxidase deficiency can result in seizures and coma and can be life-threatening. However, affected individuals who survive infancy generally have a normal life expectancy, and the signs and symptoms of the disorder typically become milder or disappear by adulthood.

Corticosterone methyloxidase deficiency is a rare disorder; its prevalence is unknown. Researchers have described two types of the condition: Type I is more common in the Amish population of Lancaster, Pennsylvania, while type II is more common in people of Iranian Jewish ancestry. The two types have similar signs and symptoms but can be distinguished by laboratory testing.

Mutations in the CYP11B2 gene cause corticosterone methyloxidase deficiency. This gene provides instructions for making an enzyme called aldosterone synthase. The aldosterone synthase enzyme is found in the adrenal glands, which are located on top of the kidneys.

Aldosterone synthase helps produce a hormone called aldosterone. Aldosterone regulates blood pressure by maintaining proper salt and fluid levels in the body. The aldosterone synthase enzyme is involved in a series of three chemical reactions that produce aldosterone from other (precursor) molecules: the conversion of 11-deoxycorticosterone to corticosterone, the conversion of corticosterone to 18-hydroxycorticosterone, and the conversion of 18-hydroxycorticosterone to aldosterone.

The CYP11B2 gene mutations that cause corticosterone methyloxidase deficiency lead to insufficient production of aldosterone, which impairs the kidneys' ability to reabsorb salt (sodium chloride or NaCl) into the blood and release potassium in the urine. As a result, excessive amounts of salt in the form of charged atoms (ions) of sodium (Na⁺) and chlorine (Cl^-) leave the body in the urine, while not enough potassium is released. The resulting imbalance of ions in the body underlies the signs and symptoms of corticosterone methyloxidase deficiency.

Genetic Testing Information

• Genetic Testing Registry: Corticosterone methyloxidase type 2 deficiency
• Genetic Testing Registry: Corticosterone 18-monooxygenase deficiency

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• CORTICOSTERONE METHYLOXIDASE TYPE I DEFICIENCY
• CORTICOSTERONE METHYLOXIDASE TYPE II DEFICIENCY

Scientific Articles on PubMed

• PubMed

• Leshinsky-Silver E, Landau Z, Unlubay S, Bistrizer T, Zung A, Tenenbaum-Rakover Y, Devries L, Lev D, Hanukoglu A. Congenital hyperreninemic hypoaldosteronism in Israel: sequence analysis of CYP11B2 gene. Horm Res. 2006;66(2):73-8. doi: 10.1159/000093583. Epub 2006 May 29. Citation on PubMed
• Lopez-Siguero JP, Garcia-Garcia E, Peter M, Sippell WG. Aldosterone synthase deficiency type I: hormonal and genetic analyses of two cases. Horm Res. 1999;52(6):298-300. doi: 10.1159/000023500. Citation on PubMed
• Nguyen HH, Hannemann F, Hartmann MF, Malunowicz EM, Wudy SA, Bernhardt R. Five novel mutations in CYP11B2 gene detected in patients with aldosterone synthase deficiency type I: Functional characterization and structural analyses. Mol Genet Metab. 2010 Aug;100(4):357-64. doi: 10.1016/j.ymgme.2010.04.016. Epub 2010 May 21. Citation on PubMed
• Peter M, Dubuis JM, Sippell WG. Disorders of the aldosterone synthase and steroid 11beta-hydroxylase deficiencies. Horm Res. 1999;51(5):211-22. doi: 10.1159/000023374. Citation on PubMed
• Peter M, Fawaz L, Drop SL, Visser HK, Sippell WG. Hereditary defect in biosynthesis of aldosterone: aldosterone synthase deficiency 1964-1997. J Clin Endocrinol Metab. 1997 Nov;82(11):3525-8. doi: 10.1210/jcem.82.11.4399. Citation on PubMed
• Peter M. Congenital hyperreninemic hypoaldosteronism: are there different forms? Horm Res. 2006;66(2):79-80. doi: 10.1159/000093584. Epub 2006 May 29. No abstract available. Citation on PubMed
• Rosler A, White PC. Mutations in human 11 beta-hydroxylase genes: 11 beta-hydroxylase deficiency in Jews of Morocco and corticosterone methyl-oxidase II deficiency in Jews of Iran. J Steroid Biochem Mol Biol. 1993 Apr;45(1-3):99-106. doi: 10.1016/0960-0760(93)90128-j. Citation on PubMed
• White PC. Aldosterone synthase deficiency and related disorders. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):81-7. doi: 10.1016/j.mce.2003.10.013. Citation on PubMed