Kostmann syndrome is a condition also known as severe congenital neutropenia. It has multiple genetic etiologies, the earliest described being autosomal recessive. Patients present with severe infections early in life.
Kostmann syndrome (KS) is named after Rolf Kostmann, who reported a condition he described as infantile agranulocytosis in 1956 and it was later termed as KS . The ailment that Kostmann described is autosomal recessive. Since then, it has been discovered that KS is a genetically heterogeneous set of disease conditions, and thus the more commonly used term is severe congenital neutropenia (SCN). Modes of inheritance include autosomal dominant, autosomal recessive, X-linked, and a number of cases are sporadic. It is a rare disorder that affects both males and females in equal proportions.
Gene mutations include the gene encoding neutrophil elastase (ELA2) (the most frequent cause of SCN), colony stimulating factor 3 receptor (CSF3R) gene, and the HS1-associated protein X1 (HAX1) gene (responsible for autosomal recessive KS)  . The same genes can be affected by different mutations, hence the varying presentation and treatment outcomes .
Affected individuals suffer from a wide range of opportunistic infections at a young age, ranging from minor infections to fatal illness. Examples include gingivitis, otitis media, upper respiratory tract infections, liver abscesses, various skin infections, omphalitis, and fever. Many of these infections are bacterial, although other organisms have been identified, such as fungi. The most common bacteria cultured are the Streptococcus and Staphylococcus species.
Congenital neutropenias represent a group of disorders, usually characterized by a low neutrophil count. Other features may be present, to varying degrees, depending on the genetic origin of the illness. SCN often involves failure of neutrophils to reach maturation in the bone marrow as well  . The autosomal recessive form of KS is characterized by a more marked neutropenia than the other variants . KS may be present as a part of another disorder, such as Fanconi pancytopenic syndrome or Chediak-Higashi syndrome.
A long-term complication of KS is the higher incidence of myelodysplastic syndrome (MDS) and leukemia (acute myeloid leukemia in particular), among those affected  . The prognosis is often poor. Furthermore, the mutation in the HAX1 gene is associated with neurological impairment, manifesting as epilepsy, as well as cognitive and developmental delay .
Entire Body System
On the basis of these twins, we speculate that in preterm infants who die with bacterial sepsis, the diagnosis of Kostmann syndrome can be missed, because their neutropenia can be ascribed solely to bacterial sepsis.5 We speculate further that the reason [pediatrics.aappublications.org]
We speculate that in preterm infants who die with bacterial sepsis, the diagnosis of Kostmann syndrome can be missed, because their neutropenia can be ascribed solely to bacterial sepsis, and the underlying cause of their neutropenia is never suspected [nature.com]
Leishman’s interest is sepsis is in part because his wife Audrey is a sepsis survivor like Sophia. Sophia knows continuing with her sport it will be a difficult process, but she remains optimistic. “It’s a slow process. [gettysburgconnection.org]
A preterm infant died of group B streptococcal sepsis 7 h after birth. The infant's complete blood count showed total agranulocytosis. [ncbi.nlm.nih.gov]
- Recurrent Infection
Uncommon cause of recurrent infections. Indian J Med Paediatr Oncol 2012;33:51-3 How to cite this URL: Deotare UR, Patel PD, Parikh RP, Bhagat EA. Uncommon cause of recurrent infections. [doi.org]
Children with Kostmann’s syndrome usually present with severe and recurrent infections, mainly in the respiratory tract and skin. [chop.edu]
Kost·mann syn·drome ( kōst'wahn ), severe infantile agranulocytosis, an inherited disorder of infancy characterized by severe, recurrent infections and neutropenia. [medical-dictionary.thefreedictionary.com]
infections resulting with the demise of the patient at an earlier age. [longdom.org]
- Recurrent Bacterial Infection
Kostmann syndrome is a rare, severe, congenital neutropenia disorder characterized by a lack of mature neutrophils (absolute neutrophil counts less than 500 cells/mm3) associated with frequent, recurrent bacterial infections (e.g. otitis media, pneumonia [ebi.ac.uk]
bacterial infections (e.g. otitis media, pneumonia, sinusitis, urinary tract infections, abscesses of skin and/or liver) and increased promyelocytes in the bone marrow. [orpha.net]
Abstract Kostmann syndrome (KS) is an autosomal recessive disorder characterized by a low neutrophil count and recurrent bacterial infections, including periodontal disease. [ncbi.nlm.nih.gov]
bacterial infections from early infancy. [semanticscholar.org]
- Surgical Procedure
Appropriate antibiotics must be used for all surgical procedures, including laryngoscopy and tracheal intubation. Several drugs (and other chemicals) may induce neutropenia/agranulocytosis in even healthy people. [accessanesthesiology.mhmedical.com]
This form of skin infection is difficult to treat with antibiotics alone and typically requires a surgical procedure to remove the involved sweat glands in order to stop the skin inflammation. [livingnaturally.com]
To investigate the potential role of apoptosis in SCN, bone marrow aspirates and biopsies were obtained from 4 patients belonging to the kindred originally described by Kostmann and 1 patient with SCN of unknown inheritance. [ncbi.nlm.nih.gov]
A bone marrow aspirate showed granulocytic hypoplasia and a maturation arrest at the promyelocyte stage. Hematopoietic cell culture showed normal numbers of colony-forming units—granulocyte macrophage. [jamanetwork.com]
[…] syndrome. 14 years old male patient diagnosed during the first few months of life as Kostmann syndrome by frequent admission for bacterial infection and peripheral blood films with automated neutrophil count (ANC) range from 0.1-0.3x10(9)/L, bone marrow aspiration [longdom.org]
These four patients were all preterm (26,28,28, and 32 wks gestation), all presented with profound neutropenia during the first weeks of life, had marrow aspirates with an “arrest” at the promyelocyte or myelocyte stage, and had negative studies for isoimmune [nature.com]
Jaw & Teeth
EBV and HCMV were detected in the two subjects with Kostmann syndrome periodontitis. The results of the study indicate that nonsurgical treatment of Kostmann syndrome periodontitis can reduce supragingival and salivary herpes viral loads. [ncbi.nlm.nih.gov]
The decrease in the number of neutrophils alters the host defense capacity, causing periodontal disease to manifest at an early age, with gingival inflammation, aggressive periodontal destruction, edema, periodontal pouches, and tooth mobility. [oooojournal.net]
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Substrate cleavage was then monitored by AMC liberation in a Fluoroscan II plate reader (Labsystems, Stockholm, Sweden), with the use of 355-nm excitation and 460-nm emission wavelengths. [bloodjournal.org]
The diagnosis of Kostmann syndrome is made when blood results drawn from successive differential counts, reveal an absolute neutrophil count (ANC) below 500 cells per microliter. Bone marrow analysis showing numerous immature promyelocytes also supports the diagnosis   . Furthermore, the bone marrow biopsy may show decreased cellularity and is important in ruling out possible malignancies . Autosomal recessive KS, as described by Kostmann, has a neutrophil count less than 200 cells per microliter  .
Other features that might be present in the full blood count are anemia, in addition to elevated levels of platelets, monocytes, and eosinophils. The total white cell count remains within the average range, while the immunoglobulin G (IgG) is high. Other chemical parameters are usually normal, and patients respond normally to vaccinations. However, antinuclear antibodies (ANA) may be high if the underlying cause is autoimmune.
Genetic testing may also be conducted, in order to delineate the specific genetic mutation. Imaging modalities are sometimes used, and these include:
- Dual-energy X-ray absorptiometry (DEXA) scanning. This is done to determine bone density, as patients with KS may have osteoporosis.
[…] marrow and blood show a number of other abnormalities (including failure of neutrophil precursors to mature beyond the promyelocyte stage, and absolute increases in the numbers of monocytes, eosinophils, and platelets (monocytosis, eosinophilia and thrombocytosis [rxlist.com]
Aside from agranulocytosis, the bone marrow and blood show a number of other abnormalities (including maturational arrest of neutrophil precursors at the promyelocyte stage, absolute monocytosis, eosinophilia and thrombocytosis). [medicinenet.com]
The results of the study indicate that nonsurgical treatment of Kostmann syndrome periodontitis can reduce supragingival and salivary herpes viral loads. [ncbi.nlm.nih.gov]
Apoptosis was significantly diminished in sections obtained during treatment with G-CSF. [ashpublications.org]
Without special treatment, patients died before 2-3 years. [m.iliveok.com]
If the bone marrow is not irreparably damaged, the prognosis is good with proper treatment, and the patient will recover as the production of granulocytes resumes. [medical-dictionary.thefreedictionary.com]
The prognosis is often poor. Furthermore, the mutation in the HAX1 gene is associated with neurological impairment, manifesting as epilepsy, as well as cognitive and developmental delay. [symptoma.com]
Niemeyer, Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents, Blood, 127, 11, (1387), (2016). Kanwaldeep Mallhi, David B. Dix, Karen Y. [doi.org]
The finding of the disease associated variants in this thesis will eventually contribute to improved diagnosis, prognosis, risk assessment and a future treatment of patients. [diva-portal.org]
Prognosis With the advent of G-CSF therapy infectious deaths are rare. Approximately 10% of patients develop AML. This is associated in almost all cases with G-CSF-R mutations. [atlasgeneticsoncology.org]
Neutropenia is very common in preterm infants, and certainly very few of these will have Kostmann syndrome as the etiology. [nature.com]
It has multiple genetic etiologies, the earliest described being autosomal recessive. Patients present with severe infections early in life. [symptoma.com]
The neutropenia was ascribed to bacterial infection and no other etiologic explanations were sought. [pediatrics.aappublications.org]
In 40% of patients, a genetic etiology for severe congenital neutropenia was unknown.  Mortality/Morbidity The mortality rate is 70% within the first year of life in the absence of medical intervention with granulocyte colony-stimulating factor (G-CSF [emedicine.com]
Frequency International Epidemiological data are limited given the overlapping case definitions of congenital neutropenia and few patient registries. [emedicine.com]
Zeidan, Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges, Blood Reviews, 10.1016/j.blre.2019.04.005, (2019). [doi.org]
Pathophysiology: though the underlying genetic defect in myeloid precursor cells is not entirely elucidated, mutations in the gene (ELA2) encoding neutrophil elastase appear to be present in most patients. [bionity.com]
[…] include: Homeostasis and migration of neutrophil granulocytes,Granulocyte-colony Stimulating Factor (G-CSF) receptor signaling,New Granulocyte-colony Stimulating Factor (G-CSF) Receptor Signaling Pathways ,Neutrophil elastase (ELANE) – Genetics and Pathophysiology [books.google.com]
The purpose of this project was to improve the understanding of the clinical course and the pathophysiology of autosomal recessive SCN. [openarchive.ki.se]
She has an active role in Public Education to minimize and control inherited blood diseases, environmental pollution and cancer prevention. Email: [email protected] [longdom.org]
Comprehensive and up-to-date, Hematopoietic Growth Factors in Oncology: Basic Science and Clinical Practice offers an integrated survey of the role of HGFs in treating and preventing anemia, neutropenia, and thrombocytopenia in patients with malignant [books.google.com]
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She has an active role in Public Education to minimize and control inherited blood diseases, environmental pollution and cancer prevention. Email: [email protected] PDF HTML [omicsonline.org]
Tea tree oil : Tea tree oil is purported to have antiseptic properties, and has been used traditionally to prevent and treat infections. [livingnaturally.com]
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