APA (Old Order Amish; Eastern Pennsylvania)

Inheritance: autosomal recessive
Genes: CYP11B2

Aldosterone deficiency I
CMO I deficiency
Aldosterone deficiency due to defect in steroid 18-hydroxylase

Salt wasting
Failure to thrive
Growth retardation
Dehydration
Fever

Corticosterone Methyloxidase Type I Deficiency

Clinical Characteristics

General description (for patients):

This condition leads to salt wasting and electrolyte imbalance in children beginning as early as several weeks of age.  If not treated, severe dehydration may result.  There may be increased susceptibility to infection.

Medical description:

This adrenal cause of salt wasting results from a defect in one of the steps of aldosterone biosynthesis, the 18-hydroxylation of cortisone (B) to 18-hydroxycorticosterone (18-OHB).  The decrease in aldosterone can lead to hyperkalemia, hyponatremia, and metabolic acidosis resulting in failure to thrive and growth retardation.  Severe dehydration and intermittent fever may also occur.  The ratio of corticosterone to 18-OHB is elevated, just the reverse of an allelic disorder, CMO type II, in which the next enzyme in the cascade, 18-oxidase, is deficient.  Those patients surviving infancy have a milder disease as another mineralocorticoid, 22-deoxycorticosterone, aids in maintaining electrolyte balance.

Genetics:

A mutation in the CYP11B2 gene on chromosome 8 (8q21) causes this disorder via a defect in the corticosterone methyloxidase enzyme. The same gene also codes for steroid 18-hydroxylase (P-450C18).  This is an autosomal recessive disorder which has been found among the Lancaster County, Pennsylvania, Amish secondary to a five base pair deletion in the CYP11B2 gene.

Treatment:

Mineralocorticoid supplements have been reported to be helpful.  Over time the new endproduct, 11-deoxycorticosterone (DOC) is accepted as the new mineralocorticoid diminishing the need for exogenous mineralocorticoid.

Prognosis:

Variable as a result of variations in mutations.  Few families have been reported.

Ancillary treatments and support:

Electrolyte monitoring.

Specialists and speciality centres:

Pediatricians, endocrinologist.

References:

Mitsuuchi, Y., Kawamoto, T., Miyahara, K., Ulick, S., Morton, D.H., Naiki, Y., Kuribayashi, T., Toda, K., Hara, T., and Orii, T., Yasuda, K., Miura, K., Yamamoto, Y., Imura, H., and Shizuta, Y.:  Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients.  Biochem. Biophys. Res. Commun.  190: 864-869, 1993. PubMed ID: 8439335

Peter, M., Fawaz, L., Drop, S.L.S., Visser, H.K.A., and Sippell, W.G.:  Hereditary defect in biosynthesis of aldosterone: aldosterone synthase deficiency 1964-1997.  J. Clin. Endocr. Metab. 82: 3525-3528, 1997.  PubMed ID: 9360501

Resources:

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