Neutropenia
Severe congenital neutropenia (ELA2, HAX1, GF11) - This disease is charcterised by persistent severe neutropenia from birth.
X-linked hyper IgM - Patients frequently develop neutropenia (over 60% of patients). This can be chronic and exacerbated by acute infections. Neutropenic patients can develop oral ulcers and gingivitis. Bone marrow biopsy typically reveals a block in maturation at the pro-myelocyte to myelocyte stage.
X-linked agammaglobulinemia - Neutropenia is a finding in 10% of patients at initial presentation (typically in the setting of acute infections). The neutropenia resolves following treatment of the acute infection.
WHIM syndrome - Patients present with neutropenia, hypogammaglobulinemia, and cutaneous warts. This disease is caused by mutations in the chemokine receptor CXCR4. This results in the retention of mature neutrophils in the bone marrow (myelokathexis).
Reticular Dysgenesis - Patients have a T-B-NK- SCID phenotype as well as profound neutropenia. The neutropenia is unresponsive to G-CSF. Patients typically present with a classic SCID phenotype during infancy (FTT, candidiasis, diarrhea, severe viral infections).
WAS (mutations in the Cdc42-binding site) - Mutations in the Cdc42 binding site of the Wiskott-Aldrish syndrome protein can result in a form of X-linked neutropenia. These patients do not have thrombocytopenia, eczema, or humoral/T cell immunodeficiency. WASP protein expression is typically normal.
Chediak-Higashi syndrome - Patients develop neutropenia which may be the result of intramedullary destruction. Neutrophils also contain giant granules due to defective vesicle transport. Additional disease features include skin hypopigmentation, bleeding disorder, neurologic abnormalities, and an HLH-like “accelerated phase”.
Griscelli syndrome Type 2 - Patients have mild neutropenia and markedly decreased NK cell and T cell cytotoxicity. Unlike CHS, neutrophils do not contain giant granules.
Hermansky-Pudlak Syndrome Type 2 - Patients have chronic neutropenia and markedly decreased NK cell and T cell cytotoxicity. Unlike CHS, neutrophils do not contain giant granules.
Dyskeratosis Congenita - Patients may develop progressive bone marrow failure as a result of defective telomere maintenance. Patients can develop anemia, thrombocytopenia, neutropenia, and combined immunodeficiency.
Schwachman-Diamond syndrome - This disease is characterized by bone marrow failure (with neutropenia), pancreatic insufficiency, and metaphyseal chondrodysplasia.
Fanconi pancytopenia - This is an AR inherited bone marrow failure syndrome that results in anemia and thrombocytopenia. Neutropenia secondary to marrow failure occurs in 95% of patients (T and B cell immunity is normal). Additional features include short stature, radial hypoplasia, microcephaly, renal and genital anomalies, skin hyperpigmentation, mental retardation, and characteristic facial features.
DNA Ligase IV patients have a combined immunodeficiency, growth retardation, and bird-like facies. In addition, pancytopenia from bone marrow failure has been described in some patients.
Glycogen storage disease Ib - Patients present with severe hypoglycemia, lactic acidosis, and hepatomegaly. The majority (87%) of patients develop chronic or intermittent neutropenia.
Transcobalamin II deficiency - Patients develop macrocytic anemia, thrombocytopenia, and neutropenia. Immunologic abnormalities include neutropenia, lymphopenia, hypogammaglobulinemia, and impaired specific antibody responses. Replacement therapy with hydroxycobalamin can reverse the clinical manifestations of this disease. “