APA (Old Order Amish; Eastern Pennsylvania)

Inheritance: autosomal recessive
Genes: CYP11B1

Congenital adrenal hyperplasia
Steroid 11-beta-hydroxylase deficiency
11-beta-hydroxylase deficiency
P450C11B1 deficiency
Adrenal hyperplasia hypertensive form

Androgen excess
Hypertension
Female virilization
Sexual ambiguity
Tall stature
Hypokalemia
Early male puberty

Adrenal Hyperplasia IV

Clinical Characteristics

General description (for patients):  

This is a hormonal disorder caused by an excess of androgen, a male hormone.  As a result, females often have genitalia resembling that of males and as many as half are erroneously raised as such.  Puberty occurs early and rapidly in males.  Patients may be excessively tall.  High blood pressure due to retention of salt can be a serious threat to health.

Medical description:  

Adrenal hyperplasia IV is associated with marked virilization and severe, early-onset systemic hypertension.  It is a significant cause of erroneous gender assignment with perhaps half of females being raised as males until the onset of menses.  Puberty is early and aggressive in males.  Excessive production of steroid precursors such as 11-deoxycortisol, and 11-deoxycorticosterone (DOC) leads to salt retention and hypervolemic hypertension. Hypokalemia is a threat.  There is also decreased synthesis of cortisol and corticosterone.  The amount of virilization and blood pressure levels are not necessarily correlated.

Genetics:  

A defective 11-beta-hydroxylase resulting from a mutation in the CYP11B1 gene on chromosome 8 (8q21) causes this form of adrenal hyperplasia.  It is an autosomal recessive disorder resulting from an excess of androgen and its precursors causing virilization and systemic hypertension.  This condition is primarily found in Jewish and Arabic families throughout the Middle East but a mutation (1343G>A) in CYP11B1 has been reported in the Amish of Pennsylvania.

Treatments: 

Hydrocortisone therapy can be helpful in slowing growth but hypertension may persist and require aggressive treatment.

Prognosis:

Hormonal regulation is key to managing signs and symptoms.

Ancillary treatments and support:  

Karyotyping may be necessary in cases with ambiguous genitalia and certainly in newborn offspring of families in which the gene is known to segregate.

Specialists and specialty centers:

Endocrinologist, pediatrician, urologist, cardiologist.

References:

White, P.C., Dupont, J., New, M.E., Leiberman, E., Hochberg, Z., and Rosler, A.:  A mutation in CYP11B1 (arg448-to-his) associated with steroid 11-beta-hydroxylase deficiency in Jews of Moroccan origin.  J. Clin. Invest. 87: 1664-1667, 1991. PubMed ID: 2022736

Al-Jurayyan, N.A.M.:  Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency in Saudi Arabia: clinical and biochemical characteristics.  Acta Paediat. 84: 651-654, 1995.  PubMed ID: 7670248

Resources:

Congenital Adrenal Hyperplasia Network

Associated Graphics