Analysis of Chronic Granulomatous Disease in the Kavkazi Population in Israel Reveals Phenotypic Heterogeneity in Patients with the Same NCF1 mutation (c.579G>A).

PURPOSE: Chronic granulomatous disease (CGD) is an innate immune deficiency disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex that impair the synthesis of oxygen radicals, thus rendering patients susceptible to recurrent infections and excessive hyperinflammatory responses. The most common autosomal recessive form of CGD is p47phox deficiency, which is often clinically milder than the more common X-linked recessive form. Here, we report data on genetics, clinical and biochemical findings in 17 CGD patients of Kavkazi origin with the nonsense mutation c.579G>A in the NCF1 gene, leading to p47phox deficiency. METHODS: Diagnosis was based on detailed clinical evaluation, respiratory burst activity by cytochrome c reduction and dihydrorhodamine-1,2,3 (DHR) assay by flow cytometry, expression of p47phox by immunoblotting and molecular confirmation by DNA sequence analysis. RESULTS: Twelve male and five female patients with median age at onset of 2.5 years (range 1 day to 9 years) were included in the study. The present cohort displays an encouraging 88% overall long-term survival, with median follow-up of 17 years. Clinical manifestations varied from mild to severe expression of the disease. Correlation between genotype and phenotype is unpredictable, although the Kavkazi patients were more severely affected than other patients with p47phox deficiency. CONCLUSIONS: Kavkazi CGD patients harbor a common genetic mutation that is associated with a heterogeneous clinical phenotype. Early diagnosis and proper clinical management in an experienced phagocytic leukocyte center is imperative to ensure favorable patient outcome. New treatment strategies are ongoing, but results are not yet conclusive.

A Case of Immunoglobulin Deficiency with increased IgM / 대한내과학회지

Immunoglobulin deficiency with increased IgM, as defined by World Health Organization classification of primary immunodeficiency, is characterized by normal or increased concentrations of serum IgM and, in some cases, IgD, but decreased or absent IgG, IgA, and IgE. Patients with these disorders have a high incidence of recurrent pyogenic infections, including otitis media, pneumonia, and septisemia. We recently experienced a case of immunoglobulin deficiency with increased IgM in a 25-year old man. He had been suffered from recurrent pyogenic infections-pneumonia, otitis media-since about 6 months of his age. He was admitted due to pneumonia, and Haemophilus influenza was isolated from the sputum culture. Also chest X-ray showed bronchiectasis. His serum immunoglobulin levels revealed increased concentration of IgM and decreased IgG and IgA. He was successfully treated with antibiotics, and now he is being followed-up. So we present this case with the review of literature.