Каллман синдромы: дамудың тоқтауы және иіс сезудің жоқтығы

Kallmann syndrome (KS) is a genetic disorder that prevents a person from starting or fully completing puberty. Kallmann syndrome is a form of a group of conditions termed hypogonadotropic hypogonadism. To distinguish it from other forms of hypogonadotropic hypogonadism, Kallmann syndrome has the additional symptom of a total lack of sense of smell (anosmia) or a reduced sense of smell. If left untreated, people will have poorly defined secondary sexual characteristics, show signs of hypogonadism, almost invariably are infertile and are at increased risk of developing osteoporosis. The condition is more commonly diagnosed in males than in females. A 2011 study of the Finnish population produced an estimated incidence of 1 in 48,000 people overall, with 1 in 30,000 for males and 1 in 125,000 for females. Kallmann syndrome was first described by name in a paper published in 1944 by Franz Josef Kallmann, a German American geneticist. The link between anosmia and hypogonadism had already been noted by Spanish doctor Aureliano Maestre de San Juan in 1856.

Genetics of GnRH deficiency conditions. To date at least 25 different genes have been implicated in causing Kallmann syndrome or other forms of hypogonadotropic hypogonadism through a disruption in the production or activity of GnRH (37). These genes involved cover all forms of inheritance and no one gene defect has been shown to be common to all cases which makes genetic testing and inheritance prediction difficult. The number of genes known to cause cases of KS/CHH is still increasing. The ANOS1 gene defect (previously known as KAL 1) was the first one discovered and the one most commonly tested for. It causes the x linked form of Kallmann syndrome and is associated with the additional symptoms of anosmia, bimanual synkinesis and renal agenesis. This defect is thought to be responsible for between 5 and 10% of all Kallmann syndrome/CHH cases. The term hypogonadism describes a low level of circulating sex hormones; testosterone in males and oestrogen and progesterone in females. Hypogonadism can occur through a number of different mechanisms. The use of the term hypogonadotropic relates to the fact that the hypogonadism found in HH is caused by a disruption in the production of the gonadotropin hormones normally released by the anterior pituitary gland known as luteinising hormone (LH) and follicle stimulating hormone (FSH).

Diagnosing KS and other forms of CHH is complicated by the difficulties in distinguishing between a normal constitutional delay of puberty or a case of KS/CHH. The diagnosis is often one of exclusion found during the workup of delayed puberty. In males, the use of age appropriate levels of testosterone can help to distinguish between a case of KS/CHH from a case of delayed puberty. If no puberty is apparent, especially no testicular development, then a review by a reproductive endocrinologist may be appropriate. If puberty is not apparent by the age of 16 then the person should be referred for endocrinological review. Post natal diagnosis of KS/CHH before the age of 6 months is sometimes possible as the normal post natal hormonal surge of gonadotropins along with testosterone or oestrogen is absent in babies with KS/CHH. This lack of detectable hormones in the blood can be used as a diagnostic indicator, especially in male infants. In females, diagnosis is sometimes further delayed as other causes of amenorrhoea normally have to be investigated first before a case of KS/CHH is considered. Diagnosis of KS/CHH normal involves a range of clinical, biochemical and radiological tests to exclude other conditions that can cause similar symptoms.

Comparing height to standard growth charts. Determining the Tanner stage of sexual development. (Males with KS/CHH are normally at stage I or II with genitalia, females at stage I with breast development and both males and females at stage III with pubic hair development). Once this has been achieved, continued hormone replacement therapy is required for both males and females to maintain sexual function, bone health, libido and general wellbeing. In females with KS/CHH, infertility is primarily due to the lack of maturation of eggs located within the ovaries. Ovulation induction can be achieved either with pulsatile GnRH therapy or alternatively with gonadotropin injections (hCG, FSH, hMG) given at set intervals to trigger the maturation and release of the egg for natural conception.

Kisspeptin is a protein that regulates the release of GnRH from the hypothalamus, which in turn regulates the release of LH and, to a lesser extent, FSH from the anterior pituitary gland. Kisspeptin and its associated receptor KISS1R are known to be involved in the regulation of puberty. Studies have shown there is potential for kisspeptin to be used in the diagnosis and treatment of certain cases of Kallmann syndrome and CHH.