Diseases

Kostmann Syndrome – Causes, Symptoms & Treatment

Kostmann Syndrome

Kostmann syndrome is a congenital and severe neutropenia characterized by the absence of neutrophilic granulocytes . Without these components of the immune system, patients with the syndrome are far more susceptible to infection than average. Long-term administration of G-CSF is an option as a therapeutic measure.

What is Kostmann Syndrome?

A subset of white blood cells is known as neutrophils. These leukocytes belong to the non-specific and innate immune system and are involved in both phagocytosis and exocytosis of granules. Accordingly, the neutrophilic granulocytes absorb larger, extracellular particles and eliminate them.

They also smuggle out foreign substances and pollutants and thus take on important tasks in the immunological defense against pathogens. Kostmann syndrome is a symptom complex caused by absent neutrophilic granulocytes. The disease is present from birth and has a genetic cause. The syndrome was first described by the Swedish physician Kostmann in the 20th century.

The case of the first description corresponded to a family in which six children were affected by the disease. At the time, Kostmann called the syndrome infantile genetic agranulocytosis. The term Kostmann syndrome was only later used in honor of the person who first described it. Kostmann syndrome is one of the neutropenias .

Decreases in neutrophilic granulocytes are summarized as such. Within the neutropenia, Kostmann syndrome is considered to be a severe and congenital form that is associated with reduced resistance to infections .

causes

As a congenital neutropenia, Kostmann syndrome has a genetically inherited basis. There is less than one case for every 300,000 newborns. The symptom complex is therefore described as extremely rare. However, Kostmann himself was able to summarize factors in the cases examined that speak for a hereditary basis.

The most decisive factor in this context is the fact that the family studied by Kostmann had six children with the symptom complex. Later cases of the syndrome were also able to show that the inheritability of the disease often leads to several cases in the same family. Only a few cases were isolated sporadic diseases. The German pediatrician Klein identified the causative gene for Kostmann’s syndrome long after Kostmann’s first description.

This gene is HAX 1, which is affected by a mutation in patients with the syndrome and thus disrupts the fixed process within cells. The identified gene regulates apoptosis and thus programmed cell death. For this reason, the mutation of the gene creates a severe limitation in connection with myelopoiesis and thus the maturation of white blood cells.

Symptoms, Ailments & Signs

Patients with Kostmann syndrome suffer from infections much more frequently than average because of the lack of neutrophils. Because of this immunodeficiency , Kostmann syndrome becomes apparent shortly after birth in most cases.

A few days after birth, infections with bacterial pathogens often occur, which spread quickly and are particularly severe. In most cases, abscesses also form . After the second year of life, accompanying symptoms such as erosive gingivitis or aggressive periodontitis often develop in the patient’s oral cavity. Fever is a common accompaniment to these processes.

Some of those affected also suffer from osteoporosis . The extent to which there is a connection between the two diseases has not yet been finally clarified. The patient’s immune deficiency can also appear as general weakness and exhaustion , which is only crowned by the aforementioned susceptibility to infections.

Diagnosis & disease progression

The diagnosis of Kostmann syndrome is made by laboratory tests. In laboratory diagnostics, Kostmann syndrome manifests itself as severe neutropenia. In order to secure the suspicion of the syndrome, a molecular genetic examination can take place, which provides evidence of the mutation of gene HAX 1 and thus confirms the suspected diagnosis.

A favorable diagnosis now applies to patients with Kostmann syndrome. However, this connection has only been valid since the discovery of antibiotic therapy. Before this breakthrough, the syndrome was associated with an unfavorable prognosis and mostly fatal outcome.

complications

Due to Kostmann syndrome, those affected usually suffer from a severely weakened immune system. Infections and inflammations occur more frequently, so that the quality of life of those affected is significantly reduced. The wound healing of the patients is also restricted and delayed by the Kostmann syndrome. The syndrome often leads to the formation of abscesses.

Those affected often suffer from fever and are therefore restricted in their everyday lives. Especially in children, the Kostmann syndrome can lead to limitations in development and significantly delay it. In most cases, there is also general weakness and a significantly reduced resilience. Those affected often appear tired and exhausted and no longer actively participate in everyday life.

Treatment of Kostmann syndrome takes place with the help of antibiotics and other drugs. There are no particular complications or complaints. However, those affected also need a bone marrow transplant to fully complete the treatment. The life expectancy of the patient remains unchanged if the treatment is successful. However, it is not uncommon for the parents of those affected to suffer from psychological problems or depression and also need psychological support.

When should you go to the doctor?

The Kostmann syndrome cannot be treated causally so far. Nevertheless, the disease must be clarified and treated at an early stage in order to avoid any long-term consequences. Parents who notice abscesses, recurring fever and other signs of Kostmann syndrome in their child should consult the pediatrician immediately. If there are other symptoms, such as gingivitis or periodontitis, medical advice is also required. If there are signs of osteoporosis, a specialist must be consulted. Since the disease is an enormous burden for the children, physiotherapeutic treatment is always necessary.

The family doctor can refer the parents to a specialist and, if necessary, a psychologist . This is necessary above all in the case of serious illnesses, as these also demand a lot of strength from the relatives. If the child loses consciousness or develops a serious infection, an ambulance must be called. The same applies to falls as a result of an attack of weakness. In any case, Kostmann syndrome requires immediate clarification and treatment by a doctor. Any depression and personality changes need to be treated by a therapist.

Treatment & Therapy

A causal treatment is not yet available for Kostmann syndrome. However, causal therapies for genetic mutations are now a subject of medical research. It is possible that gene therapy treatment methods will exist in the future. So far, the syndrome has mainly been treated symptomatically. In the case of acute infections, antibiotic treatment takes place to disable the pathogens.

As long-term therapy, treatment with G-CSF is an option for patients with Kostmann syndrome. This is a granulocyte colony stimulating factor. This peptide hormone is one of the cytokines and is produced by different tissues in the human body. The G-CSF shows above all a stimulating effect on the formation of granulocytes, which takes place in the bone marrow.

In the long term, a bone marrow transplant can be considered as a therapeutic option for those affected by Kostmann syndrome. This transplantation takes place either by harvesting stem cells from a bone marrow donation, by donating peripheral blood stem cells or by donating umbilical cord blood. However, bone marrow transplants in immunocompromised patients carry a high risk of infection, such as infection with the cytomegalovirus , with pneumococci or gastrointestinal infections.

In addition, rejection reactions can occur. For these reasons, the doctor must carefully weigh up the risk and benefit of the transplantation in each individual case. If the patient’s situation is stable, for example with long-term therapy with G-CSF, the risks of the transplant outweigh the benefits that the person would derive from it.

Outlook & Forecast

Kostmann syndrome is a genetic disease. Since doctors and medical professionals are not allowed to change the genetics of humans due to legal requirements, they see themselves as being exposed to a limited area of ​​action when it comes to providing health care to those affected. Patients must seek lifelong medical treatment if they wish to achieve any change in their health.

If the medication given is discontinued over the course of life and without consulting a doctor, or if the dosage is changed, an immediate deterioration in general well-being and an increase in symptoms can be expected. In cooperation with the doctor treating you, the weakened immune system can be stabilized. Although healing does not occur, various ailments can be minimized.

Consequences are also treated symptomatically over the lifespan. These can lead to complications. In addition, the administration of medication is associated with side effects and risks. If the doctor and patient decide in favor of bone marrow transplantation based on the overall situation, the prospects for subsequent health development improve. Nevertheless, the procedure is difficult and associated with numerous complications. In addition to rejection reactions of the organism and a longer waiting time for a suitable donor, there can be other significant impairments in quality of life and well-being.

prevention

Since Kostmann syndrome is a congenital disease and the actual cause of the causative mutation of HAX 1 has not yet been clarified, the symptom complex cannot be prevented.

aftercare

As a rule, the possibilities of aftercare for Kostmann syndrome prove to be relatively difficult, since it is a genetic disease that cannot be completely cured. However, a doctor should be consulted very early on so that no further complications or symptoms can arise, since this disease usually cannot heal on its own.

In the case of a desire to have children, the person concerned should have a genetic examination and counseling carried out so that the syndrome itself cannot occur again in the descendants. In many cases, those affected with Kostmann syndrome are dependent on taking antibiotics. The instructions of the doctor should always be followed, whereby attention must also be paid to the correct dosage and regular intake.

Furthermore, regular checks and examinations by a doctor are important in order to detect further damage to the internal organs at an early stage. Those affected should protect themselves particularly well against infections and other complaints in the case of Kostmann syndrome. In some cases, despite treatment, the life expectancy of those affected by this disease is reduced.

You can do that yourself

In most cases, those affected by Kostmann syndrome are dependent on lifelong therapy, so that self-help is usually not necessary.

The symptoms of the weakened immune system can be limited relatively well by the medication, so that illnesses and infections occur less often. However, these symptoms can also be avoided by simple hygiene measures . Wearing warm clothing in winter can also prevent common illnesses. Since those affected often suffer from tiredness or general weakness, children in particular need a lot of bed rest and need to rest their bodies. In this way, diseases and complications can be avoided, especially in childhood.

Talking to other people affected by the syndrome can also help against psychological problems or depression. In adolescents or children, the disease can lead to bullying or teasing, so that therapy can also be carried out. As a rule, however, the symptoms can be very well limited with the help of medication, so that the patient’s life expectancy is not reduced. Unfortunately, Kostmann syndrome cannot be prevented.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.