Kostmann syndrome

The Kostmann syndrome is a cogenital and severe neutropenia, which is characterized by the absence of neutrophil granulocytes. Without these components of the immune system, patients with the syndrome are far more susceptible to infection than the average. Long-term administration of G-CSF is a possible therapeutic measure.

What is Kostmann Syndrome?

Patients with Kostmann's syndrome suffer from infections far more often than the average due to the lack of neutrophils. Because of this immune deficiency, Kostmann's syndrome can be recognized shortly after birth in most cases.
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A subset of white blood cells is known as neutrophils. These leukocytes are part of the unspecific and innate immune system and are involved in both phagocytosis and exocytosis of granules. The neutrophil granulocytes therefore take up larger, extracellular particles and eliminate them.

They also discharge foreign substances and pollutants and thus take on important tasks in the immunological defense against pathogens. The Kostmann syndrome is a complex of symptoms caused by a lack of neutrophil granulocytes. The disease exists from birth and has a genetic cause. The syndrome was first described by the Swedish doctor Kostmann in the 20th century.

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

Reductions in neutrophil granulocytes are summarized as such. Within the neutropenia, Kostmann's syndrome is a severe and congenital form that is associated with a reduced defense against infections.

causes

As cogenital neutropenia, Kostmann syndrome has a genetic hereditary basis. There is less than one case for every 300,000 newborns. The symptom complex is therefore called extremely rare. However, Kostmann himself was able to summarize factors in the investigated cases that speak for a hereditary basis.

The most decisive factor in this context is the fact that the family examined by Kostmann had six children with the symptom complex. Later cases of the syndrome have also shown that the inheritance of the disease often leads to multiple cases in the same family. Only a few cases were isolated sporadic diseases. The German pediatrician Klein identified the causative gene for Kostmann 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 defined process within cells. The identified gene regulates apoptosis and thus programmed cell death. For this reason, the mutation of the gene creates a severe restriction in connection with myelopoiesis and thus the maturation of white blood cells.

Symptoms, ailments & signs

Patients with Kostmann's syndrome suffer from infections far more often than the average due to the lack of neutrophils. Because of this immune deficiency, Kostmann's syndrome can be recognized shortly after birth in most cases.

A few days after birth, infections with bacterial pathogens often spread rapidly and are particularly severe. In most cases, abscesses also form. After the age of two, accompanying symptoms such as erosive gingivitis or aggressive periodontitis often develop in the patient's oral cavity. Fever is a common side effect of these processes.

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

Diagnosis & course of disease

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

For patients with Kostmann syndrome, a favorable diagnosis is now valid. However, this relationship 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

Because of Kostmann's 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 patient's wound healing is also restricted and delayed by Kostmann syndrome. It is not uncommon for the syndrome to develop abscesses.

Those affected very often suffer from fever and are therefore restricted in their everyday life. Especially in children, Kostmann syndrome can lead to restrictions in development and significantly delay it. Mostly there is also a 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's syndrome takes place with the help of antibiotics and other drugs. There are no particular complications or complaints. However, people also need a bone marrow transplant for treatment to be fully completed. The life expectancy of the patient remains unchanged with successful treatment. Not infrequently, however, the parents of those affected also suffer from psychological complaints or depression and also need psychological support.

When should you go to the doctor?

The Kostmann syndrome cannot yet be treated causally. Nevertheless, the disease must be clarified and treated at an early stage in order to avoid any late effects. Parents who notice abscesses, recurrent fever, and other signs of Kostmann's syndrome in their child are best advised to consult the pediatrician immediately. If there are additional 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, also call in a psychologist. This is especially necessary in the case of serious illnesses, as these also require a lot of strength from the relatives. If the child loses consciousness or becomes seriously infected, an ambulance should be called. The same applies to falls as a result of weakness. The Kostmann syndrome always requires immediate clarification and treatment by the doctor. Any depression and personality changes must be treated by a therapist.

Treatment & Therapy

A causal treatment for Kostmann syndrome is not yet available. However, causal therapeutic approaches for genetic mutations are now a subject of medical research. In this way, gene therapy treatment options may exist in the future. So far, the syndrome has mainly been treated symptomatically. In acute infections, antibiotic treatment takes place in order to put the pathogen out of action.

Treatment with G-CSF is an option as long-term therapy for patients with Kostmann's 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. Above all, G-CSF has 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 a therapeutic option for those affected by Kostmann syndrome. This transplant takes place either by obtaining stem cells from bone marrow donation, by peripheral blood stem cell donation or by donating umbilical cord blood. Bone marrow transplants in immunocompromised patients carry a high risk of infection, for example for infection with the cytomegalovirus, pneumococci or gastrointestinal infections.

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

You can find your medication here

➔ Medicines to strengthen the defense and immune system

Outlook & forecast

The Kostmann syndrome is a genetic disease. Since doctors and medical professionals are not allowed to change human genetics due to legal requirements, they are exposed to a limited area of ​​action in providing health care for the person concerned. Patients have to seek medical treatment for life if they want to change their state of health.

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

Follow-up symptoms are treated symptomatically over the life span. 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 a bone marrow transplant based on the overall situation, the prospects of later 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 further significant impairments to quality of life and well-being.

prevention

Since Kostmann's syndrome is a cogenital disease and the actual cause of the causal mutation in HAX 1 has not yet been clarified, the symptom complex cannot be prevented.

Aftercare

As a rule, follow-up care options for Kostmann syndrome prove to be relatively difficult because it is a genetic disease that cannot be completely cured. However, a doctor should be consulted very early so that there are no further complications or complaints, as this disease usually cannot heal itself.

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

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

You can do that yourself

In most cases, those affected by Kostmann's 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 diseases and infections are less common. However, these complaints can also be avoided by simple hygiene measures. Wearing warm clothing in winter can also prevent common diseases. Since those affected often suffer from tiredness or general weakness, children in particular need a lot of bed rest and have to take care of their bodies. In this way, diseases and complications can be avoided, especially in childhood.

Discussions with other sufferers of the syndrome can also help against psychological complaints 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 limited very well with the help of medication, so that there is also no reduced life expectancy for the patient. Unfortunately, Kostmann syndrome cannot be prevented.