Starting with 19 sibships collected by kostmann 1975, iselius and gustavson 1984 assembled evidence that a single founder was responsible for the cases observed in sweden. Kostmann syndrome or infantile genetic agranulocytosis, part one. Neutropenia in pediatric practice american academy of. Kostmanns syndrome is a congenital disorder that causes an impairment of myeloid differentiation in the bone marrow characterized by severe neutropenia, which can be treated with recombinant human granulocyte colonystimulating factor gcsf. Severe congenital neutropenia kostmann syndrome is an autosomal recessive disorder caused by mutations in the hclsassociated protein x1 hax1 gene and is characterized by severe persistent neutropenia absolute neutrophil count download pdf. Infection with htlv virus may lead to a form of all 14. However, scn is genetically heterogeneous, and most cases seem to arise sporadically, consistent with its transmission as an. Kostmann syndrome is a rare, severe, congenital neutropenia disorder characterized by a lack of mature neutrophils absolute neutrophil. Sacco adolescent and young adult program for cancer and hereditary blood diseases. Severe hereditary conditions such as kostmann syndrome and certain immunodeficiency syndromes associated with neutropenia are rare, perhaps 1 per 100,000, and are more likely to present in neonates and infants, although acquired conditions such as immune neutropenia and neutropenia related to infection also occur in this age group. Download pdf in 1956 kostmann described a condition of neutropenia and repeated bacterial infections in infancy that he termed infantile genetic agranulocytosis. We enrolled related patients with morbus kostmann and unrelated patients with congenital neutropenia mild form of kostmannlike syndrome and cyclic neutropenia. Pdf rolf kostmann 19091982 was a swedish pediatrician and army doctor. Children born with this condition lack neutrophils a type of white blood cell that is important in fighting infection, also called granulocytes.
Children with the syndrome suffer frequent infections from bacteria which in the past led to death in threequarters of cases before 3 years of age. Kostmann syndrome is an inherited disease in which the number of certain white blood cells, known as neutrophils, is too low. Kostmann s syndrome is an inherited disorder of the bone marrow. Most cases of scn respond to treatment with granulocyte colonystimulating factor, which. A absolute neutrophil count anc chronically less than 500mm3 is the main sign of kostmanns.
Kostmanns disease, recombinant hugcsf, monosomy 7 and mdsaml. Kostmanns syndrome is an inherited disorder of the bone marrow. Get your full text copy in pdf american journal of case. Kostmann syndrome or infantile genetic agranulocytosis. 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. The treatment consisted of scaling and root planing. Celebrating 50 years of clinical and basic research on severe congenital neutropenia. Severe congenital neutropenia genetics home reference nih. Treatment of kostmann syndrome consists of gcsf for life. Congenital neutropenia cn includes hematologic disorders characterized by severe neutropenia with an absolute neutrophil count anc below 0. Kostmann syndrome or severe congenital neutropenia scn is a rare disease, usually diagnosed during the first months of life, characterized by extremely low levels of neutrophils in the peripheral blood, a maturational arrest of the myelopoiesis in the.
After an extensive evaluation he was diagnosed as having congenital neutropenia consistent with kostmanns s yndrome. The likely origin of the gene was thought to be the parish of overkalix in the county of norrbotten in the most northern part of sweden. A 15yearold yemeni patient diagnosed during the first few months of his life with kostmann s syndrome. People with this condition have a shortage deficiency of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The nonsurgical management of a patient with kostmann syndrome. Kostmann syndrome an overview sciencedirect topics. Congenital neutropenia or kostmann syndrome is an inherited disorder manifesting in infancy. Gcsf receptor anomaly the intracellular carboxy terminal region was noted in a few patients 6 out of 54, initially in two patients who later developed secondary leukemia. This disease is also known as severe congenital neutropenia scn. Congenital neutropenia in man was first reported 50 years ago by the swedish paediatrician rolf. Pdf the nonsurgical management of a patient with kostmann. Kostmann syndrome, or severe congenital neutropenia, is an autosomal recessive disease that affects the production of neutrophils.
Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. Without treatment, most babies born with the disorder would not survive their first. This rare syndrome is inherited as an autosomal recessive pattern and characterized by severe neutropenia. Of these, more than 95% responded to rhugcsf treatment with an increase in ancs to. Kostmann disease was first described in 1956 as an autosomal recessive disorder characterized by severe neutropenia and onset of severe bacterial infections early in life. A collection of disease information resources and questions answered by our genetic and rare. Kostmann syndrome ks is an autosomal recessive disorder characterized by a low neutrophil count and recurrent bacterial infections, including periodontal disease. The term congenital neutropenia is used interchangeably although some authors argue that the term is more appropriate for sporadic cases. Kostmann was among the first to describe congenital agranulocytosis 3 when he reported static neutropenia accompanied by a promyelocytic maturation arrest in the bone marrow in a consanguineous family in sweden, with apparent autosomal recessive inheritance.
Kostmann syndrome and severe congenital neutropenia. Kostmann syndrome is a rare inherited form of severe chronic neutropenia usually detected soon after birth. Severe congenital neutropenia scn, also often known as kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. After an extensive evaluation he was diagnosed as having congenital neutropenia consistent with kostmanns syndrome. Neutrophils are instrumental in fighting off infection by surrounding and destroying bacteria that enter the body. Infantile agranulocytosis was first clearly delineated by kostmann 1956.
Kostmanns syndrome care at floating hospital for children. Periodontal disease in patients from the original kostmann. This rare blood disorder is characterized by severe chronic neutropenia. Kostmann syndrome is defined as a chronic neutropenia, dating from early childhood, characterized typically by a granulopoeisis impairment at the promyelocyte stage. Kostmann syndrome is a subtype of chronic neutropenia with onset in early childhood with an autosomal recessive pattern of development. All patients had periodontitis before gcsf treatment started, apart from the patient with cyclic neutropenia, though patients with this disorder can also have this problem. Scn manifests in infancy with lifethreatening bacterial infections. The deficiency of neutrophils, called neutropenia, is apparent at birth. Deficiency of antibacterial peptides in patients with.
He coined the term infantile genetic agranulocytosis for this condition, which is now known as kostmann syndrome. Kostmanns s yndrome is a rare congenital disorder of neutrophil production due to impairment of myeloid differentiation in the bone marrow, with the neutrophil count being characteristically less than 500. Cyclic neutropenia is a rare blood disorder characterized by recurrent episodes of abnormally low levels of neutrophils a type of white blood cell in the body. Severe congenital neutropenia autosomal recessive 3. Treatment of severe chronic neutropenia should focus on prevention of. The term, congenital neutropenia redirects to this page. 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. As these white blood cells help people fight invading bacteria, patients with kostmann syndrome are unusually vulnerable to infections.
We present the case of a yearold boy with kostmanns syndrome who was treated with recombinant human gcsf from age 3. Severe persistent neutropenia results in an increased susceptibility to frequent bacterial infections. S evere periodontitis in a patient with infantile genetic agranulocytosis kostmann syndrome is presented. It was discovered in 1956 by swedish doctor kostmann. Kostmann syndrome encyclopedia article citizendium. Symptoms, risk factors and treatments of kostmann syndrome medical condition kostmann syndrome is a group of diseases that affect myelopoiesis most. Kostmann syndrome is a severe neutropenia, the incidence varies12 cases 100.
Congenital neutropenia with extrahematopoietic manifestations kostmanns syndrome and hax1 mutations. Clinical data, cbc, pbs, bm asp pictures total 99 photos with description. Professor, tufts university school of medicine departments. Patients with kostmann syndrome severe congenital neutropenia scn typically normalize their absolute neutrophil count anc upon granulocyte colony. Kostmanns syndrome definition of kostmanns syndrome by. Congenital neutropenia cn includes hematologic disorders characterized by severe neutropenia with an absolute neutrophil count anc. Papillary thyroid carcinoma ptc is the most common type of thyroid malignancy associated with gene alterations, including in the mitogenactivated. A 12monthold boy with kostmanns syndrome was admitted with cavitary pulmonary disease.
Therefore, the eponym kostmann disease best fits this specific mutation and mode of inheritance. First described in 1956, kostmann syndrome, also called congenital neutropenia, is characterized as is characterized by an arrest of the maturation of neutrophil precursors at the promyelocytic stage of differentiation and low levels of mature neutrophils in peripheral blood. Cyclic neutropenia genetic and rare diseases information. Severe congenital neutropenia autosomal recessive 3 genetic and. It was generally lethal before treatment with granulocyte colonystimulating. In his pivotal doctoral thesis, rolf kostmann studied 14 affected children from an inbred family from the province of norrbotten, sweden. The disorder, described by rolf kostmann in 1950 and 1956 1, 2, remains a paradigm in the field of congenital neutropenia. These children suffer frequent infections from bacteria which in the past led to death in threequarters of cases before 3 years of. Case description jbl, white, male was admitted three times with recurrent pneumonia, otitis, anemia, neutropenia, eosinophilia and monocytose in peripheral blood and cord lock maturation phase pro. Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving gcsf therapy.
One definitional concept arbitrarily restricts the use of kostmann syndrome to autosomal recessive inheritance, and uses severe combined neutropenia scn as an overarching term for kostmann syndrome and autosomal dominant forms. The term kostmanns syndrome is sometimes used, inappropriately, for neutropenia with elane mutations. Kostmann syndrome definition of kostmann syndrome by. Symptoms of cyclic neutropenia may include fever, a general feeling of ill health, andor sores ulcers of the mucous. A great majority of cases are caused by sensitization to drugs or chemicals that affect the bone marrow and.
The periodontal status and treatment of the patient is described. A condition with a lack of neutrophils a type of white blood cell that is important in fighting infection. He had also had bacterial conjunctivitis, periorbital cellulitis, pneumonitis, and otitis media since the age of 10 days. Kostmanns syndrome is often considered as the paradigm of. Kostmann syndrome is severe congenital neutropenia. His umbilical cord had not fallen off until he was 3 weeks old. Severe congenital neutropenia is a group of rare diseases, characterized by a severe depletion of absolute neutrophil count which can be isolated or associated to extrahematological features neurological, endocrine, immunological, renal, etc. Director, the center for health solutions at the institute for clinical research and health policy studies. Measurement of serum granulocyte colonystimulating factor. Kostmann syndrome, or severe congenital neutropenia scn, is an autosomal recessive disorder of neutrophil production. If you have problems viewing pdf files, download the latest version of adobe reader. Autosomal recessive severe congenital neutropenia scn1 constitutes a primary immunodeficiency syndrome associated with increased apoptosis in. We present the case of a yearold boy with kostmanns.
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