Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns.

BACKGROUND: Alteration of vitamin B12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B12 deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B12) related disorders, both genetic and acquired conditions. METHODS: A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated. RESULTS: During the period 2015-2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia. CONCLUSIONS: When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.

Motivación y conocimiento de la solicitud y significado de los resultados del cribado de drogas de abuso en orina / Reasons for the request and knowledge and significance of the results of the drugs of abuse urine screening

Objetivos. Este estudio pretende evaluar el grado de conocimiento que poseen los médicos para solicitar al laboratorio las determinaciones de drogas de abuso en orina (DAU) por inmunoanálisis, concretamente si es confirmar o excluir una impresión diagnóstica y objetivar el grado de conocimiento que poseen sobre el significado del punto de corte. Material y método. Se diseñó una encuesta que constaba de 4 preguntas, 2 haciendo referencia a la motivación de la solicitud de los inmunoanálisis de DAU y 2 al significado del punto de corte. El periodo de recogida fue mayo y junio de 2010 y como requisito de los encuestados solo se consideró que realizasen su trabajo en un servicio de urgencias hospitalario. Resultados. De 244 encuestas, 199 se consideraron válidas. Un 82,9% de los encuestados realizan la solicitud de cribado de DAU siempre o casi siempre para confirmar una impresión diagnóstica y el 17,0% no las utiliza nunca o casi nunca para esta finalidad. Un 68,3% realiza la solicitud siempre o casi siempre para descartar una impresión diagnóstica. Un 31,6% no las utiliza nunca o casi nunca para esta finalidad. Un 51,2% conoce el significado de un resultado positivo y un 49,7% conoce el de un resultado negativo. Conclusiones. La solicitud de pruebas de DAU requiere conocimientos específicos tanto en motivación como para la interpretación de los resultados del análisis. Los laboratorios clínicos deberían implicarse en esta formación (AU)

Objectives. To demonstrate whether the primary reason for requesting the laboratory determinations of drugs of abuse in urine (DAU) for immunoassay is to confirm or exclude a diagnostic impression, and to determine the level of knowledge on the significance of the cut-off value. Material and methods. We designed a survey that consisted of four questions, two referring to the reasons for the request of the DAU immunoassay and two to the significance of the cut-off. The data was collected during May and June 2010, and the only requirement of the respondents was that they worked in a hospital emergency department. Results. Of 244 questionnaires received, 199 were considered valid. A large majority (82.9%) of respondents made the request for DAU screening always or almost always to confirm a diagnostic impression, and 17.0% never or rarely used it for this purpose. Drug abuse screening was always or almost always requested by 68.3% to rule out a diagnostic impression, and31.6% rarely or never used them for this purpose. The significance of a positive result was understood by 51.2%, and 49.7% understood a negative result. Conclusions. Ordering DAU tests requires specific knowledge of the reason as well as to interpret the result. Clinical laboratories should be involved in training the requesters on the significance of DAU screening (AU)