Shwachman-Diamond syndrome-neutropenia, dysplasia of the epiphysis, and pancreatic insufficiency are known as Shwachman-Diamond (or Shwachman-Bodian-Diamond or Shwachman-Diamond-Oski) syndrome. syndrome. The degree of neutropenia in this disease is highly variable, but is mostly moderate. Most patients do not require routine treatment with granulocyte colony-stimulating factor (G-CSF). Myelokathexis myelodysplastic granulocyte deficiency – A very small number of patients present with recurrent severe infections, neutropenia, and abnormal bone marrow hematopoiesis. These patients are usually severely neutropenic, although the bone marrow is hyperproliferative, suggesting impaired release of bone marrow neutrophils (kathexis=stagnation). Many cells in the bone marrow are overly lobulated, with abnormally long chromatin filament connections between nuclear lobes, abnormal shape, and contain degenerated fixation nuclei and cytoplasmic vacuoles (ie, bone marrow nullipotent granulocyte deficiency). Neutrophils exhibit accelerated apoptosis, possibly due to defective expression of Bcl-x, an apoptosis suppressor, on myeloid precursor cells. Some patients present with abnormal nucleated neutrophils in the peripheral blood with abnormal phagocytosis, chemotaxis, and respiratory burst. WHIM syndrome-bone marrow nullipotent granulocyte deficiency may be part of the WHIM syndrome (warts, hypogammaglobulinemia, infection, bone marrow nullipotent granulocyte deficiency). Genetic mutations cause mutations in the CXCR4 chemokine receptor, leading to abnormalities in apoptosis and migration and retention of mature neutrophils in the bone marrow. Clinical manifestations are diverse and include neutropenia, hypogammaglobulinemia, and warts due to human papillomavirus infection. Neutrophil counts may be increased with G-CSF and/or plerixafor. MonoMac syndrome – Although the disease is characterized by persistent heavy monocytopenia (absolute monocyte count <200), MonoMac syndrome may be accompanied by mild chronic neutropenia (absolute neutrophil count [ANC] 1500). The disease is caused by mutations in the transcription factor GATA2 and is autosomal dominant. Chediak-Higashi syndrome - Chediak-Higashi syndrome is a rare genetic disorder characterized by oculocutaneous albinism, progressive peripheral neuropathy, frequent neutropenia, and progression to fatal hemophagocytic lymphohistiocytosis. Glycogen storage disease type I - Glycogen storage disease type I, also known as hepatic glycogen accumulation disorder, is caused by microsomal glucose-6-phosphatase deficiency. It can be divided into four types: 1a, 1b, 1c, and 1d. Type 1a is due to a mutation in the G6Pase gene on chromosome 17, and types 1b and 1c are caused by a gene deletion on chromosome 11q23. Neutropenia occurs in types 1b and 1c, but only patients with type 1b develop infectious complications due to defective neutrophil function, neutropenia, and circulating neutrophil apoptosis. There is evidence that microsomal glucose-6-phosphatase transport plays a role in neutrophil antioxidant protection and that defects in transporter genes can lead to impaired neutrophil function and apoptosis. Congenital cobalamin deficiency - Many genetic defects interfere with the normal uptake, continuous cellular processing, and transport of cobalamin (vitamin B12). All present with classic megaloblastic pernicious anemia, often accompanied by mild neutropenia. Immune disorders-neutropenia is seen in approximately 25% of patients with X-linked aprotininemia and in some patients with hyperimmunoglobulin M peak syndrome. Most patients with this disease have benefit with intravenous immunoglobulin. Neutropenia may also be an abnormality of the reticulocyte system, manifesting as a severe combined immunodeficiency characterized by total leukocyte deficiency. G-CSF receptor mutations - Germline G-CSF receptor (CSF3R) mutations do not appear to play a major role in neutropenia in severe congenital neutropenia (SCN). Acquired CSF3R mutations cause acute myeloid leukemia or myelodysplastic syndromes (AML/MDS), although the pathogenesis of AML/MDS in SCN is not clear. In three series, 11 of 15 SCN patients who acquired G-CSF receptor point mutations developed AML/MDS; however, G-CSF receptor point mutations are neither a prerequisite nor a direct cause of AML/MDS development, because not all patients with AML have mutations, and mutations can occur without AML, or mutations can disappear on their own. In mice with G-CSF receptor knock-in mutations that do not develop AML, it is possible that G-CSF receptor mutations develop into AML by resisting apoptosis, giving the cells more time to develop "second strike" mutations. It is estimated that G-CSF treatment increases the risk of developing AML. Given the observed hyperproliferative response to G-CSF in mutant mice, attention must be given to patients with G-CSF receptor mutations. There is no evidence that treatment accelerates leukemia progression in mutant mice, and G-CSF may not be involved in the development of leukemia in these patients, as AML also occurs in those who are untreated. this hypothesis is supported by the fact that no one with cyclic or idiopathic neutropenia treated with G-CSF develops MDS or AML. Cyclic neutropenia - Compared to other congenital neutropenias, cyclic neutropenia tends to be less severe, but pediatric patients with cyclic neutropenia who are not treated with granulocyte colony-stimulating factor (G-CSF) are still at risk for sepsis. During neutropenia, patients with cyclic neutropenia are prone to gingivitis and oral ulcers. This disease will be discussed in detail separately. Due to the primary bone marrow failure syndrome, "congenital neutropenia" in this context refers to neutropenia at birth or after birth and refers to the following three conditions: 2. severe congenital neutropenia (SCN) 3. cyclic neutropenia. 4, Shwachman-Diamond syndrome (SDS). 5, Heavy chronic neutropenia has many additional primary genetic defects, with or without other immune deficiencies, mostly manifested as reduced bone marrow reserve and increased susceptibility to infection. 6. Patients with congenital neutropenia present clinically with oropharyngeal problems, otitis media, respiratory infections, cellulitis, and skin infections, mostly due to staphylococcal and streptococcal infections, and oral ulcers and painful gingivitis almost always present in patients aged 2 years. Patients with congenital neutropenia usually have a single neutropenia with absolute neutrophil values <500/mL. Bone marrow examination of SCN patients typically shows normal or reduced proliferation, with early myeloid "arrest" at the early/intermediate granulocyte stage. 8. The diagnosis of congenital neutropenia can be made based on the relevant clinical manifestations, although the final diagnosis depends on the genetic mutation and the results of the bone marrow examination. 9. Granulocyte colony-stimulating factor has led to a significant reduction in infection rates and improved quality of life in many SCN patients.