RESUMO
IL-2-inducible T-cell kinase (ITK) deficiency is a rare inherited immunodeficiency disease characterized by homozygous mutations in the ITK gene and the inability to control Epstein-Barr virus (EBV) infection leading to EBV-associated lymphoproliferative disorders of B cell origin. Many aspects of its clinical presentation and immunologic phenotype are still unclear to clinicians. We report on a 14-year-old female patient with complaints of an 8-month history of cough and fever. Imaging studies revealed diffuse pulmonary nodules and mediastinal lymphadenopathy. Transbronchial lung biopsy showed nonmalignant polyclonal B cell proliferation. High titers of EBV DNA were detected by PCR analysis in bronchoalveolar lavage fluid, bone marrow, and blood. Genomic analysis revealed a homozygous single base pair deletion in exon 5 of the ITK gene (c.468delT) in this patient. Treatment with rituximab (anti-CD20 mab) resulted in complete clinical remission with resolution of pulmonary lesions and a negative EBV titer in serum. All patients with EBV-associated lymphoproliferative disorders should be analyzed for mutations in ITK.
Assuntos
Infecções por Vírus Epstein-Barr/enzimologia , Pneumonia Viral/enzimologia , Proteínas Tirosina Quinases/genética , Adolescente , Anticorpos Monoclonais Murinos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Linfócitos B/virologia , Líquido da Lavagem Broncoalveolar/virologia , Tosse/diagnóstico , Tosse/tratamento farmacológico , Tosse/enzimologia , Tosse/patologia , Tosse/virologia , DNA Viral/análise , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/patologia , Feminino , Febre/diagnóstico , Febre/tratamento farmacológico , Febre/enzimologia , Febre/patologia , Febre/virologia , Humanos , Fatores Imunológicos/uso terapêutico , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/patologia , Pulmão/virologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Transtornos Linfoproliferativos/diagnóstico por imagem , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/enzimologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Mutação Puntual , Rituximab , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder. Carrier frequency studies of SMA have been reported for various populations. Although no large-scale population-based studies of SMA have been performed in Iran, previous estimates have indicated that the incidence of autosomal recessive disorder partly because of the high prevalence of consanguineous marriage is much higher in the Iranian population than in other populations. METHODS: In this study, we used a reliable and highly sensitive quantitative real-time PCR assay with SYBR green I dye to detect the copy number of the SMN1 gene to determine the carrier frequency of SMA in 200 healthy unrelated, non-consanguineous couples from different part of Iran. RESULTS: To validate the method in our samples, we determined the relative quantification (RQ) of patients with homozygous deletion (0.00) and hemyzygous carriers (0.29-0.55). The RQ in 10 of 200 normal individuals were within the carrier range of 0.31-0.57, estimating a carrier frequency of 5% in the Iranian population. CONCLUSIONS: Our data show that the SMA carrier frequency in Iran is higher than in the European population and that further programs of population carrier detection and prenatal testing should be implemented.
