A report of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency in two 46,XX sisters

Figures & data

Figure 1. Genogram and physical traits of the two sisters with 17OHD. The sisters’ progenitors and their siblings are apparently healthy, except for two infant sisters, who died from unknown causes. Not all the members are represented in the genogram in order to illustrate the consanguinity and allele inheritance of the patients. Both patients showed absence of breast development and axillary or pubic hair. Their clitoral index did not show clitoromegaly.

Table 1. Clinical characteristics of the two sisters.

Characteristics	Sister 1	Sister 2
Age (years)	22 years	24 years
Chief complaints	Primary amenorrhea, absence of secondary sexual characteristics	Primary amenorrhea, absence of secondary sexual characteristics
Weight (kg)	63.2	44
Height (m)	1.68	1.60
Body mass index (kg/m^2)	22.3	17.2
Blood pressure (average, in mmHg)	128/82	150/96
Tanner stage for breast/pubic hair	2/1	2/1
Gynecologic examination	Lack of pubic hair, no adenopathies, external infantile female genitalia, absence of labia minora fusion and clitoral index of 14 mm^2	Lack of pubic hair, no adenopathies, external infantile female genitalia, absence of labia minora fusion and clitoral index of 12 mm^2
Imaging study (US & CT scan)	Infantile uterus, small ovaries (incipient) and no tumors	Infantile uterus, small ovaries (incipient) and no tumors
Left hip bone mineral density Z-score	–3.0	–3.2
Phenotype	Female	Female

US: ultrasonography; CT scan: computed tomography.

Table 2. Laboratory and genetic analyses of the two sisters.

Characteristics (units)	Sister 1	Sister 2	Reference values
Karyotype/SRY presence	46,XX/no	46,XX/no	–
Potassium (mmol/L)	4.4	3.3 (↓)	3.5 a 5.1
Follicle stimulating hormone (IU/L)	25.28 (↑)	116.40 (↑)	Follicular phase 3.5–12.5 Ovulatory phase 4.7–21.5 Luteal phase 1.7–7.7 Postmenopausal 25.8–134.8
Luteinizing hormone (IU/L)	22.33 (↑)	71.83 (↑)	Follicular phase 2.4–12.6 Ovulatory phase 14.0–95.6 Luteal phase 1.0–11.4 Postmenopausal 7.7–58.5
Dehydroepiandrosterone (nmol/L)	0.31 (N)	0.38 (N)	0.21–42.47
Dehydroepiandrosterone-S (µmol/L)	0.0027 (↓)	0.004 (↓)	0.01–0.1
Testosterone (nmol/L)	<0.001 (↓)	<0.001 (↓)	0.003–0.017
17 β Estradiol (pmol/L)	<18.36 (↓)	<18.36 (↓)	Follicular phase 45.89–609.39 Ovulatory phase 313.87–1828.16 Luteal phase 160.79–774.58
Progesterone (nmol/L)	30.08 (↑)	42.39 (↑)	Follicular phase 0.18–2.84 Ovulatory phase 0.38–38.16 Luteal phase 5.82–76 Postmenopausal <0.16–0.4
17-Hydroxyprogesterone (nmol/L)	0.51 (N)	1.4 (N)	Follicular phase 0.3–2.42 Luteal phase 1.82–6.96 Ovulatory phase 0.91–4.24 Postmenopausal 0.39–1.54
Renine (pmol/L)	–	0.28 (N)	Upright: 0.06–0.66 Lying down: 0.04–0.57
Cortisol AM (nmol/L)	28.69 (↓)	25.38 (↓)	171.05–535.21
Aldosterone (pmol/L)	3.50 (N)	4.36 (N)	Upright: 1.11–8.60 Lying down: 0.28–4.44
Deoxycorticosterone (nmol/L)	0.06 (↑)	0.41 (↑)	0.001–0.01
Adrenocorticotropic hormone (pmol/L)	30.14 (↑)	10.74 (↑)	0–10.12
Growth hormone (µg/L)	8.0 (N)	7.96 (N)	0–8
Prolactin (pmol/L)	0.42 (N)	0.37 (N)	0.21–1.01
Thyrotropin (mIU/L)	0.0024 (N)	0.0038 (N)	0.0003–0.0042

SRY: sex-determining region Y; N: normal levels; ↓: below normal; ↑: above normal. All values in SI units.

Figure 2. Parents exhibit the same mutation as asymptomatic heterozygotes panels (a) and (b), thereby confirming the homozygosity found in the sisters’ panels (c) and (d).