MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: HSD11B2

Apparent mineralocorticoid excess
AME
11-beta-hydroxysteroid dehydrogenase type II
HSD 11 type II
HSD11B2

Hypokalemia
Hypertension
Low plasma renin activity
Alkalosis
Aldosterone deficiency
Failure to thrive
Low birth weight

Cortisol 11-Beta-Ketoreductase Deficiency

Clinical Characteristics

General description (for patients):

This is a metabolic disorder in which the metabolism of steroids is abnormal.  As a result, significant high blood pressure and low potassium is present, primarily in juveniles.  These symptoms may respond to a low sodium diet and/or sodium depleting drugs.  Early diagnosis is important for untreated patients may become comatose and even die.  Low birth weights and failure to thrive have been reported.

Medical description:  

Sodium retention, hypokalemia, and hypertension are the hallmarks of this corticosteroid disorder.  Low aldosterone and plasma renin activity are common.  It is sometimes called ‘apparent mineralocorticoid excess’ but no overproduction of mineralcorticoids can be demonstrated.  The deficiency in 11-beta-ketoreductase leads to a decreased rate of conversion of cortisol to cortisone which serves as the biochemical marker for this syndrome.  The ratio of urinary free cortisol to free cortisone correlates with the activity of renal 11-beta-HSD and is not only useful for the diagnosis of this deficiency, but as a risk factor for hypertension.  Salt restriction and administration of spironolactone may be helpful in control of hypertension.

Genetics:

11-beta-hydroxysteroid dehydrogenase is an enzyme complex that exists in several isoforms in different tissues.  Its encoding gene, HSD11B2 resides on chromosome 16 (16q22) and multiple allelic mutations have been described although in relatively few patients.  An extensively studied 13 year old female from a consanguineous Mennonite family in Kansas was found to have a homozygous 681C>G substitution.

Treatment:

A salt restricted diet and/or spironolactone can be helpful in managing the hypokalemic alkalosis and the hypertension.  Antihypertensives are rarely needed.

Prognosis:  

Can be good after adolescence with proper treatment.

Ancillary treatments and support:  

Encouragement and routine care.

Specialists and specialty centers:

Dietician, pediatrician, endocrinologist.

References:

Wilson, R.C., Dave-Sharma, S., Wei, J.-Q., Obeyesekere, V.R., Li, K., Ferrari, P., Krozowski, Z.S., Shackleton, C.H.L., Bradlow, L., Wiens, T., and New, M.I.:  A genetic defect resulting in mild low-renin hypertension.  Proc. Nat. Acad. Sci.95:10200-10205, 1998.  PubMed ID: 9707624

Ugrasbul, F., Wiens, T., Rubinstein, P., New, M.E., and Wilson, R.C.:  Prevalence of mild apparent mineralocorticoid excess in Mennonites.  J. Clin. Endocrinol. Metab. 84: 4735-4738, 1999. PubMed ID: 10599743.

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