5-alpha reductase type 2 deficiency

Of the 5-alpha reductase type 2 deficiency is a congenital disorder of male sex development due to the lack or reduced occurrence of the hormone dihydrotestosterone. The boys are usually born as supposed girls due to the impaired development of the external sexual characteristics. A clear development of the male sexual characteristics only takes place during puberty through a significantly increased testosterone level.

What is 5-alpha reductase type 2 deficiency?

The 5-alpha-reductase type 2 deficiency is a rare autosomal recessive inherited disorder, which causes a differentiation disorder of the sex development in boys.

A disruption of the metabolism of the hormone testosterone to dihydrotestosterone occurs. An intersexuality occurs, more precisely a masculine pseudohermaphroditism. The external genitals appear feminine or ambiguous, but the set of chromosomes is masculine.

causes

The cause is a genetic disorder of the testosterone metabolism. Due to the lack of the enzyme 5-alpha-reductase, not enough dihydrotestosterone is formed from testosterone in the unborn child. The hormone dihydrotestosterone has a two and a half times stronger biological activity on the androgenic receptors than testosterone itself.

In addition, dihydrotestosterone is significantly involved in the fetal development of the external genital organs, urethra and prostate. There are two genes in the human genome that code for the two isoenzymes of 5-alpha reductase. The type 1 enzyme and the type 2 enzyme are coded on chromosomes 2 and 5.

The isoenzyme 5-alpha reductase type 2 is characterized by the gene SRD5A2, which is found on chromosome 2. The type 2 5-alpa reductase occurs in high concentrations in the prostate, but also in the seminal vesicles, sebum glands, kidneys, testes and brain. These are all tissues that are sensitive to androgenic hormones. A total of over 90 different mutations of the SRD5A2 gene are known.

Symptoms, ailments & signs

The severity of the disease can vary greatly. From an outwardly completely female appearance to a clearly masculine appearance with mild symptoms of reduced masculinization. Signs of a possible 5-alpha reductase deficiency can be a micropenis, a malformation of the urethra, a so-called hypospadias, an undescended testicle or an enlarged clitoris.

Most patients either develop a female external genitalia with an enlargement of the clitoris or have a micropenis with varying degrees of severity of hypospadias. An isolated micropenis or a normal female genitalia occur rarely. In genetic girls, this metabolic disorder has no impact on gender development.

Diagnosis & course

Diagnosing newborns or children who have not yet reached puberty can be very difficult due to the great variability of the external genitals. If a 5-alpha reductase type 2 deficiency is suspected, a laboratory test is carried out. Both the amount of testosterone and dihydrotestosterone are determined and the relationship to each other is established.

This examination is repeated after stimulation with HCG, the human chorionic gonadotropin, has taken place. If there is a deficiency, the ratio of testosterone to dihydrotestosterone increases to over 10: 1, which is due to a lack of dihydrotestosterone. However, in some patients this relationship is not clearly defined, so that only an analysis of the gene that codes for 5-alpha reductase type 2 can provide definitive information.

The natural course of the disease in boys is initially characterized by the apparently female external genitals. The upbringing takes place accordingly in childhood that of a girl. During puberty, when there are profound hormonal changes, the clitoris suddenly grows into a penis and the testicles enter the scrotum.

In addition, there is the typical growth of beard, muscle mass and changes in the sebum gland. The testes can in principle produce sperm, but infertility can result from the previous undescended testicle itself or from hormonal underdevelopment of the prostate. Around 80 percent of boys continue to live as men after puberty. In women, however, the disease has no symptoms.

When should you go to the doctor?

In many cases it is relatively difficult to identify or diagnose 5-alpha reductase type 2 deficiency. However, in most cases the disease manifests itself through masculinization of the body and appearance. Should these symptoms arise, a doctor should definitely be consulted. This is especially the case when a micropenis develops or when the patient's clitoris has enlarged significantly.

A doctor should also be asked for advice with external complaints, such as increased hair growth on the skin. These symptoms usually occur during puberty. In many cases, surgical interventions can be carried out immediately after birth. However, this is only possible if the symptoms of the urethra caused by the 5-alpha reductase type 2 deficiency have been recognized at an early stage. A doctor should also be consulted in the event of sudden metabolic disorders, which occur mainly during puberty.

Doctors & therapists in your area

Treatment & Therapy

In the case of early diagnosis, it is advisable to support the establishment of male identity, as the later strong testosterone formation during puberty produces a formative male gender identity. In particular, psychosexual therapy may be necessary, as the boys affected were sometimes unknowingly raised like girls in childhood and suddenly have to reorient themselves sexually in adolescence.

Mostly at a young age, according to current doctrine between the 3rd and 18th month of life, a malformation of the urethra or an undescended testicle must be surgically repaired in order to prevent further consequences. In later life, an untreated malformation of the urethra can cause pain, inflammation or psychological stress due to the aesthetics.

A left undescended testicle can lead to infertility in men. During puberty, the hormones testosterone and dihydrotestosterone are substituted in order to ensure the normal development of external sexual characteristics. Fertility can be limited, but it can often be compensated for by artificial insemination.

In some cases the boys decide to go on living as girls after the diagnosis. Then during puberty there is a substitution with female hormones, the estrogens, and if necessary corrective operations with removal of the testicles.

Outlook & forecast

Due to the 5-alpha reductase type 2 deficiency, especially in male patients, there are disorders in the development of the sex. The male sexual characteristics usually only develop when puberty occurs. The penis is greatly reduced and a clitoris may develop.

The 5-alpha reductase type 2 deficiency can also lead to considerable psychological complaints. Children can also become victims of bullying and teasing at a young age. In many cases, metabolic disorders also occur, which make everyday life much more difficult for the person concerned.

The complaints and symptoms of 5-alpha-reductase type 2 deficiency can in most cases be treated without complications or difficulties. Surgical interventions are only necessary in rare cases. Treatment is carried out with the help of hormones.

If no treatment is given, pain and other discomfort may occur in the kidney and urethra area. Many patients also need psychological treatment. Life expectancy is not restricted by the deficiency and there are no more symptoms in adulthood.

prevention

No preventive measure to prevent the genetic disorder of testosterone metabolism is known. If there is a familial accumulation, a chromosome analysis of the affected couple can be carried out if pregnancy is planned. An analysis of the chromosome set of the unborn child can also be carried out. However, the corresponding risks of the intrauterine intervention must be weighed up, since in the worst case scenario, a miscarriage can occur.

Aftercare

In most cases there are no follow-up options for 5-alpha reductase type 2 deficiency because it is a congenital disorder that cannot be fully treated. A causal treatment is also not possible, so that those affected are dependent on purely symptomatic therapy. If the person concerned wishes to have children, advice can be useful in order to avoid passing on the 5-alpha-reductase type 2 deficiency.

However, the life expectancy of the patient is not reduced by the disease. Since the deficiency is often associated with psychological complaints, depression or other upsets, discussions with friends or with your own family are often very useful. Contact with other sufferers of 5-alpha-reductase type 2 deficiency can also be useful, as this can lead to an exchange of information that can make life easier.

Other malformations can be treated with the help of surgical interventions. After such an operation, the person concerned should rest and take it easy. You should refrain from physical exertion. In the case of serious psychological complaints that arise from bullying or teasing, however, proper psychological treatment is useful.

You can do that yourself

In the case of a known 5-alpha-reductase type 2 deficiency, self-help is of the greatest importance. Medical measures are usually carried out without complications. The necessary hormone therapy must be carefully observed by the parents of the person concerned and the attending physician should be consulted in the event of recognizable psychological or physical abnormalities.

Much more important, however, is psychological support for the children concerned. The family environment plays the biggest role here. It is advisable to consult an experienced child psychologist, both for the affected child and the parents. Attending a self-help group to share experiences should also be considered. Parents have to be of great support to their child with this genetic disease and be sensitive to gender education. In general, children should not be pressed into a fixed role model and should be allowed to deal with both genders. This is a natural phase that every child should go through for healthy psychological development.

However, in order to avoid later psychological stress, a strict upbringing according to the female role model - solely due to the optical conditions - must be prevented. Affected boys should be able to identify with their own gender right from the start. In the case of existing bullying, parents should often seek a conversation with their child and the educators involved. In educational specialist literature, parents can find suggestions on how to playfully strengthen their child's self-esteem.