Molecular analysis in Brazilian cystic fibrosis patients reveals five novel mutations.

We have performed molecular genetic analyses on 160 Brazilian patients diagnosed with cystic fibrosis (CF). Screening of mutations in 320 CF chromosomes was performed through single strand conformation polymorphism (SSCP) and heteroduplex analyses assay followed by DNA sequencing of the 27 exons and exon/intron boundaries of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The frequency of CFTR variants of T-tract length of intron 8 (IVS8 Tn) was also investigated. This analysis enabled the detection of 232/320 CF mutations (72.2%) and complete genotyping of 61% of the patients. The deltaF508 mutation was found in 48.4% of the alleles. Another fifteen mutations (previously reported) were detected: G542X, R1162X, N1303K, R334W, W1282X, G58E, L206W, R553X, 621+1G-->T, V232D, 1717-1G-->A, 2347 delG, R851L, 2789+5G-->A, and W1089X. Five novel mutations were identified, V201M (exon 6a), Y275X (exon 6b), 2686 insT (exon 14a), 3171 delC (exon 17a), and 3617 delGA (exon 19). These results contribute to the molecular characterization of CF in the Brazilian population. In addition, the identification of the novel mutation Y275X allowed prenatal diagnosis in a high-risk fetus.

Evolution of IgA deficiency to IgG subclass deficiency and common variable immunodeficiency.

FIRST REPORT: male child with repeated pulmonary infections from the age of 4 months. He was diagnosed as IgA deficiency (undetectable IgA levels) at the age of 3 years, when he presented repeated bouts of pneumonia and tonsillitis. Several immunologic evaluations were made between the ages of 4 months and 8 years. At 8 years and 9 months, the diagnosis of IgA deficiency was confirmed, and associated IgG2 and IgG4 deficiency (29.0 mg/dl y 0.01 mg/dl) with normal total IgG serum level was found. With the administration of intravenous gammaglobulin, the lung infections remitted and the subsequent clinical course has been uneventful up to now. SECOND REPORT: a boy with repeated infections since the age of 2 months. IgA deficiency was diagnosed at 1 year 7 months (undetectable serum IgA levels). At age 51/2 years, his clinical course worsened and more serious infections appeared. A new immunologic study revealed IgA deficiency associated with CD4 cell deficiency (432 cells/mm3) and normal CD3, CD19, and CD8 levels. Despite intensive antibiotic treatment and care, the child died. The findings suggest an association of IgA deficiency and common variable immunodeficiency.

Evolution of IgA deficiency to IgG subclass deficiency and common variable immunodeficiency

First report: male child with repeated pulmonary infections from the age of 4 months. He was diagnosed as IgA deficiency (undetectable IgA levels) at the age of 3 years, when he presented repeated bouts of pneumonia and tonsillitis. Several immunologic evaluations were made between the ages of 4 months and 8 years. At 8 years and 9 months, the diagnosis of IgA deficiency was confirmed, and associated IgG2 and IgG4 deficiency (29.0 mg/dl y 0.01 mg/dl) with normal total IgG serum level was found. With the administration of intravenous gammaglobulin, the lung infections remitted and the subsequent clinical course has been uneventful up to now. Second report: a boy with repeated infections since the age of 2 months. IgA deficiency was diagnosed at 1 year 7 months (undetectable serum IgA levels). At age 51/2 years, his clinical course worsened and more serious infections appeared. A new immunologic study revealed IgA deficiency associated with CD4 cell deficiency (432 cells/mm3) and normal CD3, CD19, and CD8 leves. Despite intensive antibiotic treatment and care, the child died. The findings suggest an association of IgA deficiency and common variable immunodeficiency (AU)

Primer reporte: varón con repetidas infecciones pulmonares a partir de los cuatro meses de edad, diagnosticado con deficiencia de IgA (niveles indetectables) a la edad de tres años cuando el niño tiene repetidos ataques de neumonía y tonsilitis. Varias evaluaciones inmunológicas fueron realizadas entre la edad de los cuatro meses y ocho años. Con ocho años y nueves meses se confirmó el diagnóstico de deficiencia de IgA, encontrándose asociación con déficit de IgG2 (29,0 mg/dl) y IgG4 (0,01 mg/dl) con normal IgG (395 mg/dl). Fue administrada gammaglobulina intravenosa con desaparición de las infecciones pulmonares y subsecuente mejora clínica.Segundo reporte: un niño con repetidas infecciones desde los dos meses de edad. Con un año y siete meses fue diagnosticado de deficiencia de IgA (niveles indetectables). A los cinco años y medio de edad, el rumbo clínico empeoró y aparecieron serias infecciones. La nueva investigación inmunológica reveló IgA deficiente asociada con células CD4 deficientes (432 cels/mm3) y niveles normales de CD3, CD8 y CD19. A pesar de tratamiento antibiótico y cuidados intensivos, el niño falleció. Estos datos sugieren la asociación entre deficiencia IgA e inmunodeficiencia variable común. (AU)

[Cystic fibrosis] / Fibrose cística.

OBJECTIVE: Due to the great advances recently achieved in the treatment of Cystic Fibrosis as well as to the fact that pediatricians need to have a better understanding of this disease, the authors propose an extensive review of the subject. METHODS: We selected the most outstanding publications on Cystic Fibrosis in the international literature of the recent years, with the purpose of being up-to-date and at the same time offering a practical synthesis for the readers. RESULTS: We elaborated an extensive review about Cystic Fibrosis covering the following topics: historical remarks, genetics, physiopathogenesis, microbiology of pulmonary infections, clinical manifestations, clinical and laboratorial criteria for diagnosis, differential diagnosis, treatment and prognosis.

[Kwashiorkor as early clinical manifestation in a baby with cystic fibrosis]. / Kwashiorkor como manifestação precoce em lactente com fibrose cística.

A case of cystic fibrosis in a baby presenting Kwashiorkor (edema, hypoalbuminemia and anemia ) is described. This is a very unusual presentation, easily attributed to unfavourable socio-economic conditions of the population, and classically considered a marker for severe pulmonary disease during the first year of life. Presence of severe pancreatic insufficiency is related to genotype delta F508 (homozygote) but colonization and early infection with Staphylococcus aureus and Pseudomonas aeruginosa in this baby requires further study. Cystic Fibrosis is the most frequent genetic disease among Caucasians, and early diagnosis has prognostic implications, agreed upon by all.