Rapid detection of Mmalton α1-antitrypsin deficiency allele by real-time PCR and melting curves in whole blood, serum and dried blood spot samples.

BACKGROUND: α1-Antitrypsin deficiency (AATD) is an autosomal codominant disorder associated with a high risk of developing lung and liver disease. The most common deficient alleles are known as Z and S. However, another deficient variant, called Mmalton, which causes a deficiency similar to variant Z, is considered to be the second cause of severe AATD in Spain. Nevertheless, the Mmalton allele is not recognizable by usual diagnostic techniques and therefore, its real prevalence is underestimated. We describe a rapid real-time PCR and melting curves assay designed for the detection of Mmalton AATD. METHODS: We tested the applicability of this new technique for the identification of the Mmalton allele in AATD screening using whole blood, dried blood spot (DBS) and serum samples. Mmalton heterozygote and homozygote samples and samples without this allele were included in the study. RESULTS: This new assay is able to detect homozygous and heterozygous genotypes in the same reaction and in a single step, giving matching results with those obtained by SERPINA1 gene sequencing. CONCLUSIONS: This technology is optimal for working with small amounts of DNA, such as in DBS and even with residual DNA present in serum samples, allowing improvement in routine algorithms of AATD diagnosis or large-scale screening. This method will be useful for obtaining more in depth knowledge of the real incidence of the Mmalton variant.

The Lambda Variant in Argentina: Analyzing the Evolution and Spread of SARS-CoV-2 Lineage C.37.

The second wave of COVID-19 occurred in South America in early 2021 and was mainly driven by Gamma and Lambda variants. In this study, we aimed to describe the emergence and local genomic diversity of the SARS-CoV-2 Lambda variant in Argentina, from its initial entry into the country until its detection ceased. Molecular surveillance was conducted on 9356 samples from Argentina between October 2020 and April 2022, and sequencing, phylogenetic, and phylogeographic analyses were performed. Our findings revealed that the Lambda variant was first detected in Argentina in January 2021 and steadily increased in frequency until it peaked in April 2021, with continued detection throughout the year. Phylodynamic analyses showed that at least 18 introductions of the Lambda variant into the country occurred, with nine of them having evidence of onward local transmission. The spatial--temporal reconstruction showed that Argentine clades were associated with Lambda sequences from Latin America and suggested an initial diversification in the Metropolitan Area of Buenos Aires before spreading to other regions in Argentina. Genetic analyses of genome sequences allowed us to describe the mutational patterns of the Argentine Lambda sequences and detect the emergence of rare mutations in an immunocompromised patient. Our study highlights the importance of genomic surveillance in identifying the introduction and geographical distribution of the SARS-CoV-2 Lambda variant, as well as in monitoring the emergence of mutations that could be involved in the evolutionary leaps that characterize variants of concern.

Miositis aguda asociada a infección por virus influenza. Serie de casos en un hospital pediátrico / Acute myositis associated with influenza infection. Case series in a pediatric hospital

La miositis aguda benigna asociada a influenza es una complicación esporádica. En Argentina, en el año 2022, hubo un aumento temprano de la circulación de influenza y del número total de las notificaciones, con la aparición de miositis secundarias. Serie clínica retrospectiva de nueve pacientes pediátricos que consultaron por dolor e impotencia funcional de extremidades inferiores, y enzimas musculares elevadas, en el hospital Pedro de Elizalde de la Ciudad Autónoma de Buenos Aires, entre agosto y octubre del 2022. En todos se detectó infección por virus influenza y se recuperaron sin secuelas. La miositis aguda benigna es una entidad infrecuente en la infancia, cuyo diagnóstico es predominantemente clínico y de recuperación ad integrum. Debe ser sospechada en pacientes con clínica compatible en contexto de alta circulación viral. La vigilancia epidemiológica aporta herramientas para identificar los virus circulantes y sus posibles complicaciones.

Benign acute myositis associated with influenza is a sporadic complication. In Argentina, in 2022, there was an early increase in influenza circulation and the total number of notifications, with the appearance of secondary myositis. Retrospective clinical series of nine pediatric patients who consulted for pain and functional impotence of the lower extremities, and elevated muscle enzymes, at the Pedro de Elizalde hospital in the Autonomous City of Buenos Aires, between August and October 2022. In all of them, infection by influenza virus and recovered without sequelae. Benign acute myositis is a rare entity in childhood, whose diagnosis is predominantly clinical and recovery ad integrum. It should be suspected in patients with compatible symptoms in a context of high viral circulation. Epidemiological surveillance provides tools to identify circulating viruses and their possible complications.

Laboratory Diagnosis by Genotyping.

Alpha-1 antitrypsin (AAT) genotyping is useful to confirm the clinical diagnosis of AAT deficiency and determine the specific allelic variant. Genotyping is the reference standard procedure for identifying rare allelic variants and characterizing new variants. It is also useful when there is a discrepancy between the patients' AAT levels and their phenotypes. AAT genotype is determined by an allele-specific genotyping assay for the S, Z, and Mmalton variants and by exome sequencing.