17α-hydroxylase deficiency diagnosed in early infancy caused by a novel mutation of the CYP17A1 gene.
BACKGROUND
Mutations of the CYP17A1 gene cause 17α-hydroxylase deficiency (17OHD) resulting in 46,XY disorder of sex development, hypertension, hypokalemia and absent pubertal development. It is a rare, autosomal recessive form of congenital adrenal hyperplasia (CAH).


METHODS
We report on a neonate with prenatally determined 46,XY karyotype. At 20 weeks of gestation, lack of development of male external genitalia was noticed. A phenotypically female child was born at 41 weeks of gestation.


RESULTS
Postnatal ultrasound revealed testes in both labia majora, an absence of uterus and normal adrenal glands. Steroid hormone analysis in serum revealed low basal levels of cortisol, testosterone and androstenedione in the presence of massively elevated corticosterone at the age of 2 weeks. The urinary steroid profile from spot urine showed excessive excretion of 17-desoxysteroids, decreased glucocorticoid metabolites and absent C19 steroids, thus proving 17OHD. Molecular analysis identified a novel mutation of the CYP17A1 gene: c.896T>A (p.I299N) in exon 5. Substitution with hydrocortisone was started. The child is raised as a girl and is developing well so far.


CONCLUSIONS
Herein, we report the unusually early diagnosis of a newborn with the rare CAH form of 17OHD allowing an early start of treatment.
Department of Obstetrics and Gynecology, Henriettenstiftung, Children's and Youth's Hospital AUF DER BULT, Hannover, Germany.
Christina
C
Petri
Stefan A
SA
Wudy
Felix G
FG
Riepe
Paul-Martin
PM
Holterhus
Jens
J
Siegel
Michaela F
MF
Hartmann
Alexandra E
AE
Kulle
Maik
M
Welzel
Joachim
J
Grötzinger
Ralf L
RL
Schild
Sabine
S
Heger
D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000235:genetics / Q000652:urine; D000328:Adult; D005091:Exons; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000097:blood / Q000235:genetics / Q000652:urine; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011247:Pregnancy; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D013256:Steroids / Q000097:blood / Q000652:urine
D013256:Steroids; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase