Pre-implantation Genetic Testing in Inherited Metabolic Diseases? Stateof- the-art and current challenges.

INTRODUCTION: Inborn errors of metabolism (IEM) are genetic diseases involving congenital disorders of enzyme activities. Most follow Mendelian autosomal recessive inheritance and few follow mitochondrial inheritance. In many cases, after the birth of an affected child parents discover that have been the carriers for the condition and worry about the risk of recurrence in future offspring. Preimplantation genetic testing (PGT) can analyze embryos before their transfer to the uterus and prevent the transmission of hereditary conditions to descendants, however this procedure is of limited value in mtDNA conditions. METHODS: The list of diseases currently approved for PGT were reviewed. The process for eligibility, was as for the Comissão Nacional Procriação Medicamente Assistida (CNPMA), of Portugal (PT). Review of international practices for Assisted Reproductive Techniques (ART) in IEM was carried out. RESULTS: As of 07.2022, 23 IEM diseases associated with deleterious variants in nDNA were approved for PGT in PT. Couples at risk for conditions not included in the list can solicit an evaluation from an expert committee, after a medical genetics consultation. To qualify for approval, diseases must cause significant suffering and/or premature death. Due to a greater number of solicitations many more IEM conditions have been approved for PGT across the world. ART for mtDNA is not available in PT. International expert centers include PGT for specific well documented variants and mitochondrial donation. CONCLUSION: PGT is a reliable approach to reduce the risk of transmission of a genetic condition to the offspring. The list of IEM disorders currently accepted for this technique in Portugal are small, but it is expanding, as many more diseases fit the necessary criteria. While appealing in theory, low success rates coupled with limited availability can be discouraging for patients. Genetic counselling is of paramount importance after the diagnosis of IEM diseases. It is important for both clinicians and patients to be made aware of the available reproductive options and their limitations.

Determinación de la concentración de óxido nítrico alveolar en aire espirado: procedimiento y valores de referencia en personas sanas / Determining the Alveolar Component of Nitric Oxide in Exhaled Air: Procedures and Reference Values for Healthy Persons

La producción de óxido nítrico (NO) se describe mediante un modelo bicompartimental que relaciona la producción y la movilidad de NO desde los alvéolos hacia las vías aéreas. La espiración a múltiples flujos permite deducir la concentración alveolar de NO (CaNO), marcador indirecto del estado inflamatorio de las zonas distales del pulmón. El objetivo fue determinar los valores de referencia de CaNO. En 33 individuos sanos se determinaron la concentración espirada de NO (FeNO) a 50ml/s y la CaNO a 10, 30, 100 y 200ml/s mediante un sensor de quimioluminiscencia (NIOX Aerocrine). El valor medio (± desviación estándar) de FeNO fue de 15±6ppb y de CaNO fue de 3,04±1,30ppb. Los valores de CaNO obtenidos en individuos sanos permitirán analizar el comportamiento inflamatorio alveolar en procesos respiratorios y sistémicos(AU)

Nitric oxide (NO) production has been described using a 2-compartment model for the synthesis and movement of NO in both the alveoli and the airways. The alveolar concentration of NO (CaNO), an indirect marker of the inflammatory state of the distal portions of the lung, can be deduced through exhalation at multiple flow rates. Our objective was to determine reference values for CaNO. The fraction of exhaled NO (FeNO) was measured in 33 healthy individuals at a rate of 50mL/s; the subjects then exhaled at 10, 30, 100, and 200mL/s to calculate CaNO. A chemiluminescence analyzer (NIOX Aerocrine) was used to perform the measurements. The mean (SD) FeNO was 15 (6)ppb. The mean CaNO was 3.04 (1.30)ppb. These values of CaNO measured in healthy individuals will allow us to analyze alveolar inflammatory behavior in respiratory and systemic processes(AU)

Metodología estadística en los estudios de comparación de métodos de medida. Respuesta de los autores / No disponible

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Determinación de óxido nítrico en aire espirado (FENO) mediante un equipo portátil (NIOX-MINO® Aerocrine) en población sana / Measurement of fraction of exhaled nitric oxide with the portable NIOX-MINO monitor in healthy adults

La determinación de óxido nítrico en aire espirado (FENO) es una técnica no invasiva que se utiliza en la evaluación clínica y el tratamiento del asma. El objetivo de este estudio ha sido determinar los valores de referencia de FENO en un grupo de voluntarios sanos mediante la utilización de un nuevo equipo portátil (NIOX-MINO® Aerocrine), así como determinar el grado de relación que presenta con el equipo de determinación habitual en nuestro laboratorio de función pulmonar (sensor de quimioluminiscencia N-6008® SIR). Según los resultados obtenidos, los valores de FENO que da el equipo portátil son siempre superiores a los que ofrece el sensor habitual, con un valor de corte de 34 ppb (media + 2 desviación estándar). Existe un relación directa y significativa de la determinación de FENO entre ambos equipos (r = 0,92; p = 0,001) con un factor de corrección de: FENO (NIOX-MINO®) = 10 + 1,5 FENO (N-6008®). La relación entre los valores de FENO y la edad, el sexo, el índice de masa corporal y los valores espirométricos no fue estadísticamente significativa

Measurement of the fraction of exhaled nitric oxide (FENO) provides a noninvasive way to monitor asthma treatment in clinical practice. The aim of this study was to determine FENO reference values for measurements recorded with the portable NIOX MINO monitor in a group of healthy volunteers. We also assessed the association between values recorded by the portable monitor and the N-6008 chemiluminescence analyzer used in our pulmonary function laboratory. The FENO values obtained with the portable monitor were consistently higher than those recorded by the N-6008 analyzer; the cutoff value for the portable monitor was 34 ppb (mean + 2 SD). We detected a direct correlation (r=0.92) between the FENO measurements recorded by the 2 monitors (P=.001). The following equation expresses the relationship between measurements from the 2 devices: FENO(NIOX MINO) = 10 + [1.5 FENO(N-6008)]. We did not observe statistically significant correlations between FENO measurements and age, sex, body mass index, or spirometry