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A deficiência de alfa-1 antitripsina (DAAT) é um distúrbio genético raro causado por uma mutação no gene SERPINA1, que codifica o inibidor de protease alfa-1 antitripsina (AAT). A DAAT predispõe os indivíduos a DPOC e doença hepática. O diagnóstico precoce é essencial para a implementação de medidas preventivas e para limitar a carga da doença. Embora diretrizes nacionais e internacionais para o diagnóstico e manejo da DAAT estejam disponíveis há 20 anos, mais de 85% dos casos não são diagnosticados e, portanto, não são tratados. No Brasil, os motivos para o subdiagnóstico da DAAT incluem o desconhecimento dos médicos sobre a condição, a diversidade racial da população, o fato de os níveis séricos de AAT serem avaliados em um número limitado de indivíduos e a falta de ferramentas diagnósticas convenientes. O diagnóstico da DAAT baseia-se em resultados de exames laboratoriais. A abordagem diagnóstica padrão envolve a avaliação dos níveis séricos de AAT, seguida de fenotipagem, genotipagem, sequenciamento gênico ou suas combinações para detecção da mutação específica. Nos últimos 10 anos, novas técnicas foram desenvolvidas, oferecendo uma alternativa rápida, minimamente invasiva e confiável aos métodos tradicionais de teste. Um desses testes disponíveis no Brasil é o teste de genotipagem A1AT, que analisa simultaneamente as 14 mutações mais prevalentes da DAAT usando DNA extraído de swab bucal ou de sangue em papelfiltro. Esses avanços podem contribuir para a superação do problema do subdiagnóstico no Brasil e em outros países, bem como podem aumentar a taxa de detecção da DAAT e, portanto, mitigar os malefícios do diagnóstico tardio. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ⩽ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results: Of the 926 COPD patients studied, 85 had DBS AAT levels ⩽ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%). In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions: The prevalence of A ATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients. [ABSTRACT FROM AUTHOR]

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Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder caused by a mutation in the SERPINA1 gene, which encodes the protease inhibitor alpha-1 antitrypsin (AAT). Severe AATD predisposes individuals to COPD and liver disease. Early diagnosis is essential for implementing preventive measures and limiting the disease burden. Although national and international guidelines for the diagnosis and management of AATD have been available for 20 years, more than 85% of cases go undiagnosed and therefore untreated. In Brazil, reasons for the underdiagnosis of AATD include a lack of awareness of the condition among physicians, a racially diverse population, serum AAT levels being assessed in a limited number of individuals, and lack of convenient diagnostic tools. The diagnosis of AATD is based on laboratory test results. The standard diagnostic approach involves the assessment of serum AAT levels, followed by phenotyping, genotyping, gene sequencing, or combinations of those, to detect the specific mutation. Over the past 10 years, new techniques have been developed, offering a rapid, minimally invasive, reliable alternative to traditional testing methods. One such test available in Brazil is the A1AT Genotyping Test, which simultaneously analyzes the 14 most prevalent AATD mutations, using DNA extracted from a buccal swab or dried blood spot. Such advances may contribute to overcoming the problem of underdiagnosis in Brazil and elsewhere, as well as being likely to increase the rate detection of AATD and therefore mitigate the harmful effects of delayed diagnosis.

Objective: To validate and develop an immunonephelometric assay for the determination of alpha-1 antitrypsin (AAT) levels in dried blood spots from COPD patients in Brazil., Methods: We determined AAT levels in serum samples and dried blood spots from 192 COPD patients. For the preparation of dried blood spots, a disk (diameter, 6 mm) was placed into a tube, eluted with 200 µL of PBS, and stored overnight at 4ºC. All of the samples were analyzed by immunonephelometry in duplicate. We used the bootstrap resampling method in order to determine a cut-off point for AAT levels in dried blood spots., Results: The correlation coefficient between the AAT levels in serum samples and those in dried blood spots was r = 0.45. For dried blood spots, the cut-off value was 2.02 mg/dL (97% CI: 1.45-2.64 mg/dL), with a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 95.7%, 27.2%, and 100%, respectively., Conclusions: This method for the determination of AAT levels in dried blood spots appears to be a reliable screening tool for patients with AAT deficiency.