Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance.

PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. METHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. RESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. CONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.

[Hyper IgE syndrome. Opportune diagnosis and management]. / Sindrome de hiper IgE. Diagnóstico y manejo oportunos.

The hyperimmunoglobulin E syndrome was discribed for Buckley, and it also called the Job syndrome. There are two types: dominant autosomal and recessive autosomal. It is a primary, rare and complex immunodeficiency, characterized clinically by recurrent skin abscesses for Staphylococcus aureus, recurrent pneumonia, and pneumatoceles, hypereosinophylia, high serum levels of immunoglobulin E (> 2,000 Ul/mL), early eczema and late loss of primary dentition. Recently a STAT3 mutation has been described as origin of dominant autosomal hyperimmunoglobulin E syndrome. Since 1972, 250 cases have been reported around the world. The diagnosis is done with the Grimbacher criteria and the prognosis depends on the opportune diagnosis and treatment. The incidence is same in women and men. The differential diagnosis is with allergic bronchopulmonary aspergillosis, chronic granullomatose disease, T cell lymphoma, and atopic dermatitis. The treatment is with prophylactic antibiotic, intravenous immunoglobulin or recombinant INF gamma.

[Increased knowledge of ARIA and GINA guides 2006 to general physicians by an educational intervention]. / Incremento del conocimiento de las guías ARIA y GINA 2006 para médicos generales mediante una intervención educativa.

BACKGROUND: Educational strategies look for the increase of knowledge in physicians; they are a useful resourse for the diffusion among physicians of guides GINA and ARIA. OBJECTIVE: To evaluate a course shop-like for physicians as an educative strategy. PARTICIPANTS AND METHODS: A transversal study was performed, where knowledge was evaluated to primary contact physicians about recent currents of guides of GINA and ARIA 2006. RESULTS: There was a participation of 69 primary contact physicians who applied a questionnaire of 30 questions: 20 about asthma (GINA) and 10 about allergic rhinitis (ARIA) before and after a course shop-like for physicians; there was improvement on calification after educative strategy on knowledge about asthma and allergic rhinitis with a p = < 0.05. CONCLUSION: The educative strategy proposed as course shop-like for primary contact physicians is effective for teaching the guides of GINA and ARIA 2006.

[Anxiety and depression in asthmatic adults in comparison to healthy individuals]. / Ansiedad y depresión en asmáticos adultos en comparación con sujetos sanos.

BACKGROUND: Asthmatic patients present different degrees of anxiety and depression, being psychiatric pathologies the most frequent alterations related to this illness. In this country there is available information of asthma in children but just a few about adult patients. OBJECTIVES: To know the frequency of anxiety and depression in adult asthmatic patients, compare them with healthy individuals and determine their relationship with the severity of illness. PATIENTS AND METHODS: There were included asthmatic adults (GINA 2002) and as control group healthy individuals, using the HAD scale (Hospital Anxiety and Depression Scale) to determine the presence of anxiety and depression RESULTS: 120 patients participated, 60 in each group with a mean age of 34 years old in the group 1 (asthmatic) and 31 years old in group 2 (healthy individuals). The HAD scale results in group 1 showed that 30% of patients presented anxiety, and 8% showed depression; in group 2 18% had anxiety and 3% depression. There are more anxiety and depression in asthmatic patients than in healthy individuals, p < 0.05, correlation between depression and severity of asthma is r = 0.288. CONCLUSIONS: Anxiety is frequent in asthmatic patients, being less common the presence of depression but related with asthma severity. These results contrast with available information where up to 54% of asthmatic patient present anxiety and 30% depression, using the same scale HAD. It is necessary to identify these problems, with the object to give an integral an accurate treatment to the patient.

[Coexistent diseases in allergic asthmatic patients. A study of 100 cases]. / Enfermedades coexistentes en pacientes asmáticos alérgicos. Estudio de 100 casos.

BACKGROUND: The prevalence of asthma in Mexico is of 12% in the general population. Allergic illnesses diminish the quality of life and increase the costs of health services. In our country there is a lack of information about asthma and the concomitant presence of other allergic diseases in adults. OBJECTIVE: To identify the association of asthma with other allergic illnesses in adults. MATERIAL AND METHODS: Patients of the Allergy and Clinical Immunology Service diagnosed with allergic asthma, according to GINA, were included. The studied variables were: age, sex, and the presence of concomitant illnesses, doing a descriptive statistic analysis. RESULTS: 100 allergic asthmatic patients were included, 69% corresponded to female and 31% to male. The association with allergic illnesses was as follows: rhinitis 92%, conjunctivitis 33% and atopic dermatitis 5%. In 13% it was associated to sinusitis, which is considered an infectious illness. CONCLUSIONS: Asthma has an important association with allergic diseases, especially rhinitis. The female group, as well as the age group between the third and fourth decades of the life, were the most affected. It is important to identify the relationship between asthma and other allergenic entities in order to establish a specific treatment, to diminish medical attention costs and to improve the quality of life of the patients.