Spring has come, but he has never smelled the flowers - Kallmann syndrome

Spring flowers and autumn fruits, blossom and bear fruit

From growth to development to reproduction

Considered a complete life course

No puberty

Just like nature lacks the spring with blooming flowers

It is undoubtedly a shortcoming of life

There are such a special group of people

Their time is "frozen" on the eve of the flowers blooming

Even though the spring breeze is everywhere

They have never smelled the fragrance of flowers

No development of secondary sexual characteristics, olfactory impairment

As if I was born different from others

They are patients with Kallmann syndrome.

Often jokingly calls himself "Old K"

So what is

Slowing down the pace of their youth?

"Old K" looks like this

In March, flowers bloom on the roadside. This is the most energetic and vibrant season of the year in nature. But for Pan Longfei, a patient with Kallmann syndrome, the breath of spring can only be appreciated with his eyes. He has never experienced the ordinary fragrance and smell of flowers in other people's mouths.

In the photo, he has a sunny smile and is handsome. But he has been weak and sickly since childhood, and is thin and small compared to other children of the same age. When other boys experienced voice change, grew beards, and grew taller, he did not grow up for a long time, and was often mistaken by his classmates as a girl who dressed more neutrally at school.

He was also given many discriminatory nicknames - "sissy", "shorty", and even worse, there were times when some boys with bad intentions wanted to team up to take off his pants and get naked to see what he looked like.

These malicious actions, strange looks, discrimination and ridicule are like tight shackles that bind weak children in their own lonely and inferior world, making it difficult for them to break free.

Adolescence is "stuck"

Kallmann syndrome patients like Pan Longfei do not develop secondary sexual characteristics during puberty, and have a "model" body shape with a short upper body and long lower body, and their internal and external genitalia are in a childish state. In addition, male patients have no beard, armpit hair, pubic hair, or voice change; female patients do not develop breasts during puberty, have no armpit hair, pubic hair, or menarche.

A small number of patients have combined cleft lip, cleft palate, cryptorchidism, deafness, and color blindness. Abdominal B-ultrasound examination shows abnormal kidney morphology or only one kidney, and olfactory nerve magnetic resonance imaging shows poorly developed or absent olfactory bulb. A small number of patients have congenital heart disease, etc.; and a very small number of patients have psoriasis, epilepsy, or mental retardation.

Image source: Pea Sir

The torment that Kallmann syndrome brings to patients is not only the symptoms themselves, but also the gender feelings that make them physically and mentally exhausted. It is said that patients with this disease are "asexual people" with almost no sexual desire and no sexual ability. Even the encyclopedia has mentioned the prejudiced word "eunuch-like". Because of their physical defects, they seem to be neither men nor women. The difference in their bodies always brings a lot of strange looks and exclusion.

Male patients often lack "masculine temperament". Traditional and conservative concepts make many patients afraid to reveal their physical defects to others, and dare not ask for their marriage and family, love and understanding. At the same time, the secrecy about sex makes it difficult for them to truly accept their bodies. The traditional social concept of "three unfilial acts, the greatest of which is to have no descendants" makes them feel like they are trapped in a quagmire, unable to extricate themselves, and endure mental torture that is times more than that of ordinary people. Also because of the rarity of the disease, many patients and their families have sought medical treatment everywhere, but have been misdiagnosed, and the road to seeking medical treatment is difficult and bumpy.

Genes draw the wrong cards

The human gonad axis includes: hypothalamus (commander-in-chief) → pituitary gland (military commander) → testicles or ovaries (soldiers), which dominates development, reproduction, and maintenance of sexual characteristics. The hypothalamus secretes gonadotropin-releasing hormone (GnRH) as a command signal to the pituitary gland, which then secretes gonadotropins (FSH and LH) and transmits these two commands to the testicles or ovaries. The testicles or ovaries will begin to produce various sex hormones (androgens, estrogens) and reproductive cells (sperm, eggs) only after receiving the two commands from the pituitary gland.

Simply put, without the command from the previous level, the next level will not work.

Image source: Tencent Medical Dictionary

In the process of commanding and receiving commands, if the hypothalamus does not secrete GnRH, that is, the pituitary gland cannot secrete LH and FSH, then it will eventually cause the lowest-level soldiers - the testicles or ovaries - to stop working because they did not receive commands, and thus cannot secrete enough sex hormones to complete the transformation from boys to men and girls to women.

During embryonic development, the GnRH nerve cells that control sexual development and the olfactory nerve cells that control olfactory function are both "neighbors" and "childhood companions". They influence each other and travel together. When the olfactory nerve is underdeveloped or cannot reach the hypothalamus, the GnRH neuron cannot reach the hypothalamus and cannot secrete GnRH in the normal position. Due to the gene mutation, the two playful children did not return to their respective homes, so the development of secondary sexual characteristics and olfactory sense was affected at the same time.

In 1944, American medical geneticist Kallmann studied three families with hypogonadism and anosmia and determined that the disease was a hereditary disease. Kallmann syndrome is familial and sporadic, and has three modes of inheritance: X-linked recessive inheritance, autosomal dominant inheritance, and autosomal recessive inheritance.

In addition to gonadal dysgenesis and congenital anosmia or hyposmia, the phenotypes corresponding to different genotypes are also different, and even the phenotypes caused by the same gene mutation may be different. It has been confirmed that multiple gene mutations can cause Kallmann syndrome.

Overcoming this "level"

Although Kallmann syndrome cannot be cured, it can be treated. If active treatment measures are taken for gonadal dysgenesis caused by Kallmann syndrome, it can help patients achieve normal sexual development during puberty and retain fertility. Therefore, Kallmann syndrome emphasizes early diagnosis and early treatment.

There is currently a lack of effective causal treatment - gene therapy, and only symptomatic treatment is currently provided, mainly for hypogonadism. Unfortunately, there is currently no effective treatment for patients with complete or partial anosmia.

In terms of treatment for gonadal function, there are different treatment plans for restoring reproductive function and maintaining secondary sexual characteristics. For patients who need to have children, recombinant gonadotropin (rLH or rFSH) containing LH or FSH activity is often used abroad. Male patients can use rLH to stimulate interstitial cells (Leydig cells) to produce testosterone, and rFSH can stimulate supporting cells (Sertoli cells) and spermatogonia; female patients can use rLH to stimulate theca cells to produce androgens, and rFSH can stimulate granulosa cells to produce estradiol. Due to the high price of rLH or rFSH, hCG containing LH activity and hMG containing LH and FSH components are often used in China.

For patients who do not have fertility needs, target gland hormone replacement therapy can be given directly. Men can be given testosterone replacement to maintain secondary sexual characteristics, and women can be given estrogen/progesterone to create an artificial menstrual cycle.

In recent years, the use of GnRH pumps in patients with low gonadotropin hypogonadism has increased year by year. Its effect in restoring fertility is similar to or slightly better than that of LH/FSH dual-stimulation therapy.

According to the "2016 Expert Consensus on Gonadotropin-Releasing Hormone (GnRH) Pulse Therapy (Draft)", GnRH pulse therapy is a method that uses a miniature GnRH input device controlled by artificial intelligence to simulate the physiological pulse secretion pattern of hypothalamic GnRH by pulsed subcutaneous injection of GnRH analogs, thereby effectively stimulating the pituitary gland to secrete gonadotropin, thereby promoting gonadal development, secretion of sex hormones and gamete production, and obtaining fertility.

In 2012, Pan Longfei founded the public welfare organization for patients with Kallmann syndrome, the Old K House. They launched the public welfare activity "Old K's Walk in China", aiming to let more people know about the existence of rare diseases and understand that patients with rare diseases are a normal group through "living cases" like themselves, so that there will be no more misunderstandings about patients with rare diseases. The warmth, strength and support from each other in the team made their steps very firm.

Although Kallmann syndrome is not a fatal disease, the psychological pressure brought to patients by social discrimination and prejudice is like a sword that takes one's life. What is scary is not the disease, but the human heart. However, the ability to love and be loved is never reflected in the lower body. A kind and tolerant heart is the weapon to overcome this "level" together.

A rare patient, in addition to the pain caused by the disease

He was no different from most people.

We both yearn for love and love life.

We all have the right to pursue our dreams and go far away

I wish every "Old K"

Everyone can enter the spring of growth and feel the "fragrance" of life

【1】Li Peipei, Lu Rongmei, Lin Wei, Huang Huibin, Liang Jixing, Li Liantao, Lin Lixiang, Chen Gang, Wen Junping. Clinical management of Kallmann syndrome[J]. Chinese Journal of Endocrinology and Metabolism, 2018, 34(01): 72-76.

【2】Marie Alnæs, Knut Olav Melle. Kallmann syndrome[J]. Tidsskr Nor Laegeforen. 2019: 139(17).

【3】Maione Luigi, Dwyer Andrew A, Francou Bruno et al. GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. [J] .Eur. J. Endocrinol., 2018.

【4】Liu Mengying. Genetic research on Kallmann syndrome[D], 2013

【5】Expert consensus on gonadotropin-releasing hormone (GnRH) pulse therapy (draft), 2016.