*For medical professionals only
It turned out to be suffering from this disease...
Written by | MSHK
Source | "Pediatric Channel of the Medical Profession" public number
Recently, a piece of news caught my attention, a 10-year-old girl Jing Jing went to the hospital for abnormal blood pressure, the doctor found that Jing Jing did not have a uterus and ovaries, and found a mass of suspected testicular tissue on the inner thigh.
Figure 1 Screenshot of source news
For ten years, Jing Jing has been raised as a girl, how can there be a suspected male feature?
In order to find out the reason, the doctor let Jing Jing do genetic testing, genetic testing, the results are shocking, the test results indicate that Jing Jing's biological sex is male! This made Jingjing's parents dumbfounded.
Doctors explained to Jing's parents that Jing had a rare congenital adrenal hyperplasia (CAH), called 17-α hydroxylase deficiency. This is also the cause of jingjing blood pressure abnormalities, if not timely intervention and treatment will trigger a hypertensive crisis, and even there is a risk of sudden death.
What is CAH?
CAH is a class of autosomal recessive disorders in which an inherited deficiency of enzymes necessary in various hormone production pathways of the adrenal cortex leads to impaired synthesis and accumulation of intermediate products, secondary to increased compensatory secretion of hypothalamic corticotropin releasing hormone (CRH) and pituitary corticotrophic hormone (ACTH), A group of disorders that cause adrenal hyperplasia [1].
Genetic diseases, not necessarily in the family of similar patients to call genetic diseases, caused by changes in genetic material or controlled by the disease-causing gene are called genetic diseases, so it is important to ask about family medical history. CAH is an autosomal recessive disorder, mostly parents each have a chromosome containing a disease-causing mutation, itself does not occur, when they both pass this chromosome to offspring, offspring will be sick, this disease often has no family history. This is also the reason why Jingjing's parents are not sick, but Jingjing is sick.
How many types of CAH are there?
CAH can be divided into five types according to the location of P450 enzyme defect:
(1) 21-hydroxylase deficiency;
(2) 11-β hydroxylase defects;
(3) 17-α hydroxylase/17,20-lyase deficiency;
(4) 3-β steroid dehydrogenase defects;
(5) Lipid-like adrenal hyperplasia.
The most common of these is 21-hydroxylase deficiency, which accounts for about 90%-95% of CAH. It is followed by 11-β hydroxylase deficiency, which accounts for about 5% of CAH. The 17-α hydroxylase deficiency in the news is very rare, with an estimated incidence of 1 in every 50,000 to 100,000 people, accounting for about 1% of CAH [2].
What causes 17-α hydroxylase deficiency?
What's the performance?
17-α hydroxylase deficiency is caused by a mutation in the CYP17 gene, resulting in partial or complete deficiency of 17α-hydroxylase, which plays two roles in the synthesis of steroid hormones:
(1) 17-hydroxylation reaction can catalyze progesterone alcohol and progesterone hydroxylation, if this enzyme deficiency can lead to increased production of deoxycorticosterone (DOC), cortisol and 18-hydroxycorticone production, the above hormones have a mineralocorticoid and glucocorticoid-like effect, can compensate patients with cortisol deficiency, patients have no adrenal insufficiency after birth, but when overcompensated, salt corticosteroid-like action leads to hyporenergic hypertension, hypokalemia.
(2) 17,20-lysis reaction can catalyze the lysis of 17 hydroxyprogesterone and 17 oxyprogesterone, and finally produce sex hormones, which lead to insufficient synthesis of sex hormones, resulting in gonadal naïveté and loss of secondary sex characteristics [3].
Typical clinical manifestations of 17-α hydroxylase deficiency are hyporenin hypertension, hypokalemia, male pseudogexual malformations and female naïveté, low androgen levels, and increased luteinizing hormone and follicle-stimulating hormone.
Jing Jing went to the hospital for abnormal blood pressure, and was detected to have 17-α hydroxylase deficiency.
Figure 2 Source network
Patients are mostly female in gender and can be divided into 46XX and 46XY according to chromosomal karyotype, of which 46XX type is less common [4]. Patients with 46XX present with underdeveloped secondary sexual characteristics, primary amenorrhea, and naïve uterus, while patients with 46XY present with pseudo-hermaphroditic malformations, feminization of external genitalia, and loss of testicles, uterus, and ovaries in the abdominal or inguinal region [3]. The hospital test results showed that Jingjing's karyotype was 46XY, so the doctor said that Jingjing's biological sex was male.
What is the effect of 17-α hydroxylase deficiency on fertility?
Women with 17-α hydroxylase deficiency have normal sexual development during the fetal period, the internal and external genital structures can develop normally, and the disease is often delayed until puberty due to hypogonadic hypogonadism.
Infertility is due to disorders of estrogen synthesis and high serum progesterone levels, ovulation disorders, uterine hypoplasia, and underdevelopment of the endometrium [5]. Currently, women with 17-α hydroxylase deficiency are largely unable to conceive naturally [6].
How is 17-α hydroxylase deficiency diagnosed clinically?
The clinical symptoms of the disease are diverse, and the diagnosis is difficult, and it is necessary to comprehensively diagnose from the clinical manifestations (such as salt loss manifestations, hyperandrogenemia, etc.), auxiliary tests (such as decreased cortisol, elevated ACTH, elevated androgens, etc.) and genetic testing.
Various precise molecular genetic tests have been used to diagnose 17-α hydroxylase deficiency, with second-generation sequencing (NGS) being one of the most important diagnostic techniques for 17-α hydroxylase deficiency [3].
How is hydroxylase deficiency treated for 17-α?
Treatment of 17-α hydroxylase deficiency is predominantly corticosteroid replacement therapy and symptomatic therapy. Gender selection and treatment requires further communication between parents and specialists to decide, and most of them are still retaining the female gender of the patient.
Glucocorticoids primarily inhibit ACTH, improve androgen levels, lower DOC levels, improve hypertension and hypokalemia, and also help promote epiphyseal closure[2].
Glucocorticoid replacement therapy can be dexamethasone, prednisone, and hydrocortisone, of which hydrocortisone belongs to the physiological glucocorticoids and has a certain water and sodium retention effect (mineralocorticoid-like effect), so the clinical application is more extensive [3].
bibliography:
Jiang Min, Bao Mingjing, Long Enwu, Tao Xue, Yang Yan.1 case of drug therapy and pharmacological monitoring of patients with 17α-hydroxylase deficiency[J/OL].Chinese Journal of Hospital Pharmacy:1-4[2022-04-18].
Hu Ying, Shi Lixin, Zhang Miao, Xu Jing.Diagnosis and treatment of 17-α hydroxylase/17,20-lyase deficiency and related literature review[J].Guizhou Medicine,2020,44(03):459-461.
[XI Ke-wang,LI Shan,TANG Xu-lei,FU Song-bo,LI Juan,CHENG Jianguo.Genetic testing analysis of a child clinically diagnosed with 17-α hydroxylase/17,20-lyase deficiency and their parents and brothers[J].Shandong Medicine,2022,62(06):30-34.
[4] ZHANG Chun-mei, YANG Rui, LI Rong, QIAO Jie, WANG Hai-ning, WANG Ying.46XX-17α-hydroxylase deficiency fertility success[J/OL].Journal of Peking University (Medical Edition):1-13[2022-04-18].
[5] Gomes L G , Bachega T A , Mendonca B B . Classic congenital adrenal hyperplasia and its impact on reproduction[J]. Fertility and Sterility, 2019, 111(1):7-12.
Pan Ping,Yang Dongzi. Advances in the understanding of fertility problems in rare enzyme defect type congenital adrenal hyperplasia[J].Journal of Practical Obstetrics and Gynecology,2021,37(06):412-414.
Source: Pediatrics Channel of the Medical Professions
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