DGM (Dutch-German Mennonite)

Inheritance: autosomal recessive
Genes: CYP17 P450C17 enzyme

APC
Congenital Adrenal Hyperplasia
17-a-hydroxylase deficiency
Combines 17-a-hydroxylase/17,20-lyase deficiency
CYP17

Hypertension
Hypokalemic alkalosis
Sexual ambiguity
Amenorrhea
Pubertal delay
Ambiguous genitalia
Hirsutism

Adrenal Hyperplasia V

Clinical Characteristics

General description (for patients):  

This is one of several hormonal disorders caused by abnormal functioning of the adrenal gland. The result can be severe imbalances in electrolytes, and often genital abnormalities.  This one, type V, can cause high blood pressure and life-threatening changes in blood potassium levels.  The genitalia may be ambigious at birth, and pubertal changes may not occur.  Females don’t menstruate and some males develop female secondary sexual characteristics.   

Medical description:  

This form of adrenal hyperplasia is secondary to 17, or combined 17, 20-lyase deficiency causing systemic hypertension, sometimes hypokalemic alkalosis, and usually genital and pubertal abnormalities.  Production of corticosterone and deoxycorticosterone is excessive.  Gender assignment may be difficult at birth.  Primary amenorrhea, atrophy of the ovaries and uterine hypoplasia have been reported.  Hirsutism and other evidence of gonadal dysfunction are often seen.

Genetics: 

 This molecular basis for this disease and other variants of hypdroxylase deficiency are enzymatic  and hence likely to be autosomal recessive.  This seems to be confirmed by the rare reported families.  Specifically, the combined 17-alpha-hydroxylase/17,20 lyase deficiency of type V adrenal hyperplasia has been reported in two Mennonite families (not known to be related), in whom both sets of parents were consanguineous.  The mutation consisted of a four base duplication in exon eight of the CYP17 gene on chromosome 10 (10q24.3).  These Canadian Mennonites were of Netherland and East Russian origin and their genomic profiles would be unlike other Swiss-German Anabaptist descendents.

Treatments:  

Attempts to normalize adrenal hormones might be of benefit for metabolic stabilization but the genital abnormalities are likely to persist.  The number of reported cases is too small to draw valid conclusions.  Karyotypes are useful to determine gender.

Prognosis:  

Patients can live to adulthood but sexual maturation remains a problem.

Ancillary treatments and support:  

Normalization of daily functions as possible

Specialists and specialty centers:

Endocrinologist, pediatrician, urologist, obstretician

References:

Kagimoto, K., Waterman, M.R., Kagimoto, M., Ferreira, P., Simpson, E.R., and Winter, J.S.D.:  Identification of a  common molecular basis for combined 17-alpha-hydroxylase/17/20-lyase deficiency in two Mennonite families.  Hum. Genet. :82: 285-286, 1989. PMID: 2786493

Geller, D.H., Auchus, R.J., Mendonca, B.B., and Miller, W.L.:  the genetic and functional basis of isolated 17,20-lyase deficiency.  Nature Genet.  17: 201-205, 1997.   PMID: 9326943

Resources:

Congenital Adrenal Hyperplasia Network

Associated Graphics