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1.
Respir Med Case Rep ; 24: 58-62, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29977761

RESUMO

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. This genetic disorder is mainly associated with development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here we report a very rare alpha-1 antitrypsin Null Q0cairo homozygous mutation characterized by a complete absence of alpha-1 antitrypsin in the plasma, in a non-consanguineous Moroccan family. This mutation has been previously described in heterozygosis in only three cases worldwide: an Italian/Egyptian family and two Italian families (Zorzetto et al., 2005). The main clinical features in two members of this Moroccan family were the severity and precocity of bronchiectasis, quickly spreading and seriously limiting respiratory function and physical activity by the second decade of age. Moreover, the index case presented with many episodes of pulmonary infections concomitant with severe neutropenia. The third member of the family presented with ankylosing spondyloarthritis and developed panniculitis later but had no respiratory symptoms. The presence of this alpha-1-antitrypsin Q0cairo homozygous mutation could explain the severity of clinical manifestations. Moreover, our observations highlight a great variability of clinical expression for the same mutation: early severe bronchiectasis, panniculitis, rheumatologic manifestations. This study further underlines the importance of genotyping by whole SERPINA1 gene sequencing in addition to serum alpha-1 antitrypsin determination, to enable detection of alpha-1 antitrypsin deficiency due to rare genotypes.

2.
Pan Afr Med J ; 26: 212, 2017.
Artigo em Francês | MEDLINE | ID: mdl-28690727

RESUMO

Hyper IgM syndrome is a well known genetic (primary) immunodeficiency disorder which was first described in 1961. It is caused by B lymphocyte deficiency characterized by normal or elevated serum IgM levels and low or zero levels of IgG, IgA, IgE resulting from isotype-switching deficiency. Clinical manifestations are dominated by recurrent infections, especially involving the digestive tube of the ENT sphere and the lungs. This syndrome is caused by B-cell immunoglobulin class switch deficiency and decreased capacity to induce proliferation of T lymphocytes. The net result of these deficiencies is reflected in increased susceptibility to Pneumocystis jiroveci, Cryptosporidium spp and other intracellular organisms as well as high rate of bacterial and viral infections. This study aimed to illustrate the importance of understanding the pathophysiological mechanisms associated with this increased susceptibility to infections in order to allow a better diagnosis and therapy in patients with Hyper IgM syndrome (HIM).


Assuntos
Linfócitos B/imunologia , Síndrome de Imunodeficiência com Hiper-IgM/fisiopatologia , Infecções Oportunistas/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/imunologia , Imunoglobulina M/sangue , Lactente , Masculino , Marrocos , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/microbiologia , Linfócitos T/imunologia
3.
J Clin Immunol ; 36(3): 187-94, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26931785

RESUMO

PURPOSE: X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) gene defect. XLA patients have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes. This multicenter study reports the clinical, immunological and molecular features of Bruton's disease in 40 North African male patients. METHODS: Fifty male out of 63 (male and female) patients diagnosed with serum agammaglobulinemia and non detectable to less than 2% peripheral B cells were enrolled. The search for BTK gene mutations was performed for all of them by genomic DNA amplification and Sanger sequencing. RESULTS: We identified 33 different mutations in the BTK gene in 40 patients including 12 missense mutations, 6 nonsense mutations, 6 splice-site mutations, 5 frameshift, 2 large deletions, one complex mutation and one in-frame deletion. Seventeen of these mutations are novel. This large series shows a lower frequency of XLA among male patients from North Africa with agammaglobulinemia and absent to low B cells compared with other international studies (63.5% vs. 85%). No strong evidence for genotype-phenotype correlation was observed. CONCLUSIONS: This study adds to other reports from highly consanguineous North African populations, showing lower frequency of X-linked forms as compared to AR forms of the same primary immunodeficiency. Furthermore, a large number of novel BTK mutations were identified and could further help identify carriers for genetic counseling.


Assuntos
Agamaglobulinemia/genética , Expressão Gênica , Frequência do Gene , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação , Infecções Oportunistas/genética , Proteínas Tirosina Quinases/genética , Adulto , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/imunologia , Idade de Início , Argélia , Alelos , Linfócitos B/imunologia , Linfócitos B/patologia , Criança , Pré-Escolar , Estudos de Associação Genética , Aconselhamento Genético , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Heterozigoto , Humanos , Lactente , Masculino , Marrocos , Infecções Oportunistas/complicações , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Proteínas Tirosina Quinases/imunologia , Análise de Sequência de DNA , Tunísia
4.
Pan Afr Med J ; 24: 316, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28154671

RESUMO

Lead colic is a rare cause of abdominal pain. The diagnosis of lead poisoning is most often mentioned in at risk populations (children, psychotic). We report the case of a 2 year old child that was presented for acute abdomen. Abdominal plain radiograph showed multiple intra-colonic metallic particles and suggested lead poisoning diagnosis. Anamnesis found a notion of pica and consumption of peeling paint. Elevated blood lead levels (BLL) confirmed the diagnosis. The lead poisoning is a public health problem especially in children, but its manifestation by a lead colic is rare and could simulate an acute abdomen table.


Assuntos
Abdome Agudo/diagnóstico , Cólica/induzido quimicamente , Intoxicação por Chumbo/diagnóstico , Pica/complicações , Dor Abdominal/etiologia , Pré-Escolar , Humanos , Chumbo/sangue , Intoxicação por Chumbo/etiologia , Masculino , Pintura/efeitos adversos , Radiografia Abdominal
5.
Immunol Rev ; 264(1): 103-20, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25703555

RESUMO

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.


Assuntos
Suscetibilidade a Doenças/imunologia , Predisposição Genética para Doença , Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/etiologia , Mycobacterium tuberculosis/imunologia , Tuberculose/etiologia , Fatores Etários , Criança , Genes Dominantes , Genes Recessivos , Humanos , Síndromes de Imunodeficiência/diagnóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
6.
J Clin Immunol ; 34(4): 452-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24596025

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is characterized by an inability of phagocytes to produce reactive oxygen species (ROS), which are required to kill some microorganisms. CGD patients are known to suffer from recurrent bacterial and/or fungal infections from the first year of life onwards. From 2009 to 2013, 12 cases of CGD were diagnosed in Morocco. We describe here these Moroccan cases of CGD. METHODS: We investigated the genetic, immunological and clinical features of 12 Moroccan patients with CGD from 10 unrelated kindreds. RESULTS: All patients were children suffering from recurrent bacterial and/or fungal infections. All cases displayed impaired NADPH oxidase activity in nitroblue tetrazolium (NBT), dihydrorhodamine (DHR) or 2',7' dichlorofluorescein diacetate (DCFH-DA) assays. Mutation analysis revealed the presence of four different mutations of CYBB in four kindreds, a recurrent mutation of NCF1 in three kindreds, and a new mutation of NCF2 in three patients from a single kindred. A large deletion of CYBB gene has detected in a patient. The causal mutation in the remaining one kindred was not identified. CONCLUSION: The clinical features and infectious agents found in these patients were similar to those in CGD patients from elsewhere. The results of mutation analysis differed between kindreds, revealing a high level of genetic and allelic heterogeneity among Moroccan CGD patients. The small number of patients in our cohort probably reflects a lack of awareness of physicians. Further studies on a large cohort are required to determine the incidence and prevalence of the disease, and to improve the description of the genetic and clinical features of CGD patients in Morocco.


Assuntos
Aspergilose/genética , Infecções Bacterianas/genética , Doença Granulomatosa Crônica/genética , Glicoproteínas de Membrana/genética , NADPH Oxidases/genética , Adolescente , Alelos , Aspergilose/complicações , Aspergilose/imunologia , Aspergilose/patologia , Infecções Bacterianas/complicações , Infecções Bacterianas/imunologia , Infecções Bacterianas/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Genes Recessivos , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , NADPH Oxidase 2 , Linhagem
7.
PLoS One ; 6(4): e18524, 2011 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-21533230

RESUMO

BACKGROUND AND OBJECTIVES: In the last decade, autosomal recessive IL-12Rß1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rß1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. METHODS AND PRINCIPAL FINDINGS: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rß1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rß1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. SIGNIFICANCE: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rß1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity.


Assuntos
Subunidade beta 1 de Receptor de Interleucina-12/genética , Tuberculose/genética , Adolescente , Pré-Escolar , Feminino , Humanos , Lactente , Irã (Geográfico) , Masculino , Marrocos , Linhagem , Índice de Gravidade de Doença , Turquia
8.
Eur J Pediatr ; 169(9): 1069-74, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20414676

RESUMO

Major histocompatibility complex class II plays a key role in the immune response, by presenting processed antigens to CD4+ lymphocytes. Major histocompatibility complex class II expression is controlled at the transcriptional level by at least four trans-acting genes: CIITA, RFXANK, RFX5 and RFXAP. Defects in these regulatory genes cause MHC class II immunodeficiency, which is frequent in North Africa. The aim of this study was to describe the immunological and molecular characteristics of ten unrelated Moroccan patients with MHC class II deficiency. Immunological examinations revealed a lack of expression of MHC class II molecules at the surface of peripheral blood mononuclear cells, low CD4+ T lymphocyte counts and variable serum immunoglobulin (IgG, IgM and IgA) levels. In addition, no MHC class II (HLA DR) expression was observed on lymphoblasts. The molecular analysis identified the same homozygous 752delG26 mutation in the RFXANK genes of all patients. This finding confirms the association between the high frequency of the combined immunodeficiency and the defect in MHC class II expression and provides strong evidence for a founder effect of the 752delG26 mutation in the North African population. These findings should facilitate the establishment of molecular diagnosis and improve genetic counselling for affected Moroccan families.


Assuntos
Efeito Fundador , Deleção de Genes , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Imunodeficiência Combinada Severa/etnologia , Imunodeficiência Combinada Severa/genética , Fatores de Transcrição/genética , Apresentação do Antígeno/imunologia , Sequência de Bases , Contagem de Linfócito CD4 , Criança , Pré-Escolar , DNA , Feminino , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Humanos , Imunoglobulinas/sangue , Lactente , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Linfócitos/citologia , Linfócitos/imunologia , Masculino , Dados de Sequência Molecular , Marrocos/epidemiologia , Reação em Cadeia da Polimerase
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