Chromosomal Microarray in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital.

Autism spectrum disorders (ASD) comprise a group of neurodevelopmental disorders (NDD) characterized by deficits in communication and social interaction, as well as repetitive and restrictive behaviors, etc. The genetic implications of ASD have been widely documented, and numerous genes have been associated with it. The use of chromosomal microarray analysis (CMA) has proven to be a rapid and effective method for detecting both small and large deletions and duplications associated with ASD. In this article, we present the implementation of CMA as a first-tier test in our clinical laboratory for patients with primary ASD over a prospective period of four years. The cohort was composed of 212 individuals over 3 years of age, who met DSM-5 diagnostic criteria for ASD. The use of a customized array-CGH (comparative genomic hybridization) design (KaryoArray®) found 99 individuals (45.20%) with copy number variants (CNVs); 34 of them carried deletions (34.34%) and 65 duplications (65.65%). A total of 28 of 212 patients had pathogenic or likely pathogenic CNVs, representing approximately 13% of the cohort. In turn, 28 out of 212 (approximately 12%) had variants of uncertain clinical significance (VUS). Our findings involve clinically significant CNVs, known to cause ASD (syndromic and non-syndromic), and other CNVs previously related to other comorbidities such as epilepsy or intellectual disability (ID). Lastly, we observed new rearrangements that will enhance the information available and the collection of genes associated with this disorder. Our data also highlight that CMA could be very useful in diagnosing patients with essential/primary autism, and demonstrate the existence of substantial genetic and clinical heterogeneity in non-syndromic ASD individuals, underscoring the continued challenge for genetic laboratories in terms of its molecular diagnosis.

Desigualdades de género en la autoría de las principales revistas médicas españolas durante el año 2017 / Gender inequalities in authorship of the main Spanish medical journals in 2017

INTRODUCCIÓN: El objetivo del estudio es analizar la desigualdad de género en la producción científica de las revistas médicas españolas. MATERIAL Y MÉTODO: Estudio transversal de las principales revistas médicas españolas clasificadas por SCImago Journal & Country Ranking (n = 24) y sus publicaciones (n = 3.375) durante el año 2017. Se calculó la ratio mujer/hombre de autoría según revista y tipo de artículo. Los análisis bivariantes se desarrollaron con la variable dependiente tipo de artículo y las independientes: sexo, centro de trabajo y país de primeras y últimas autorías. Se realizaron modelos de regresión logística para el cálculo de las odds ratios ajustadas (ORa) con intervalos de confianza al 95% (IC 95%) del sexo de autoría según el tipo de artículo, mediante el programa estadístico R. RESULTADOS: El número total de firmantes fue 16.252 (44,2% mujeres, 53,9% hombres y 1,9% sexo no identificado). Las mujeres representaron el 46% de las primeras autorías y el 33,5% de las últimas. Las mujeres fueron primeras autoras de Editoriales con menor frecuencia que los hombres (ORa 0,39; IC 95% 0,30-0,51), pero con mayor frecuencia en los Originales (ORa 1,55; IC 95% 1,33-1,80). Las mujeres fueron últimas autoras con menor frecuencia en todos los tipos de artículos, especialmente en Editoriales (ORa 0,50; IC 95% 0,35-0,70). La ratio mujer/hombre del total de autoras y autores fue inferior a 0,80 en 10 de las 24 revistas analizadas (41,7%). CONCLUSIONES: Se demuestra la desigualdad de género en la autoría de las principales revistas médicas españolas en el año 2017, principalmente en las últimas autorías y los Editoriales

INTRODUCTION: Some studies have shown a lower female participation in scientific publications. The objective of this study is to analyse the gender inequalities in the main Spanish journals of medical publications. MATERIAL AND METHOD: Cross-sectional study of the main Spanish medical journals classified by SCImago Journal & Country Ranking (n = 24) and their publications (n = 3.375), during the year 2017. Women/men ratio in authorship was calculated for all journals and types of papers. Bivariate analyses were developed with the type of article as the dependent variable, and gender, institution, and country of the first and last authors as the independent variables. Logistic regression models were performed to calculate adjusted odds ratios (aOR) and their 95% confidence intervals (95% CI) of the types of papers according to authorship gender, institution, and country. The statistical program used was R. RESULTS: The total number of authors was 16,252 (44.2% women, 53.9% men, and 1.9% non-identified gender). Women represented 46% of the first authors and 33.5% of the last ones. Women were the first authors of Editorials less often than men (aOR 0.39; 95% CI 0.30-0.51), but more often in Originals (aOR 1.55; 95% CI 1.33-1.80). Women were the last authors with less frequency in all types of papers, especially in Editorials (aOR 0.50; 95% CI 0.35-0.70). The women/men ratio in authorship was less than 0.80 in 10 of 26 journals analysed (41.7%). CONCLUSIONS: These results show the gender inequalities in the authorship of the main Spanish medical journals in 2017, especially as first authors and Editorials

[Gender inequalities in authorship of the main Spanish medical journals in 2017]. / Desigualdades de género en la autoría de las principales revistas médicas españolas durante el año 2017.

INTRODUCTION: Some studies have shown a lower female participation in scientific publications. The objective of this study is to analyse the gender inequalities in the main Spanish journals of medical publications. MATERIAL AND METHOD: Cross-sectional study of the main Spanish medical journals classified by SCImago Journal & Country Ranking (n=24) and their publications (n=3.375), during the year 2017. Women/men ratio in authorship was calculated for all journals and types of papers. Bivariate analyses were developed with the type of article as the dependent variable, and gender, institution, and country of the first and last authors as the independent variables. Logistic regression models were performed to calculate adjusted odds ratios (aOR) and their 95% confidence intervals (95% CI) of the types of papers according to authorship gender, institution, and country. The statistical program used was R. RESULTS: The total number of authors was 16,252 (44.2% women, 53.9% men, and 1.9% non-identified gender). Women represented 46% of the first authors and 33.5% of the last ones. Women were the first authors of Editorials less often than men (aOR 0.39; 95% CI 0.30-0.51), but more often in Originals (aOR 1.55; 95% CI 1.33-1.80). Women were the last authors with less frequency in all types of papers, especially in Editorials (aOR 0.50; 95% CI 0.35-0.70). The women/men ratio in authorship was less than 0.80 in 10 of 26 journals analysed (41.7%). CONCLUSIONS: These results show the gender inequalities in the authorship of the main Spanish medical journals in 2017, especially as first authors and Editorials.

Perspectiva de género sobre los cuidados informales de las niñas y niños con enfermedades raras / Gender perspective on informal care of children with rare diseases

No disponible

Factores relacionados con la autoría de las publicaciones en Anales de Pediatría / Factors related to authorship of publications in the Anales de Pediatría

No disponible

Representación femenina en las juntas directivas de las asociaciones y sociedades de Pediatría en España / Female representation on boards of directors of paediatrics associations and societies in Spain

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Falsos positivos de C5-carnitina elevada en cribado neonatal: ¿a qué son debidos? / C5-carnitine false positive results in newborn screening: What is the cause?

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Birth Prevalence of Fatty Acid ß-Oxidation Disorders in Iberia.

Mitochondrial fatty acid ß-oxidation disorders (FAOD) are main targets for newborn screening (NBS) programs, which are excellent data sources for accurate estimations of disease birth prevalence. Epidemiological data is of key importance for the understanding of the natural history of the disorders as well as to define more effective public health strategies. In order to estimate FAOD birth prevalence in Iberia, the authors collected data from six NBS programs from Portugal and Spain, encompassing the screening of more than 1.6 million newborns by tandem mass spectrometry (MS/MS), and compared it with available data from other populations. The participating NBS programs are responsible for the screening of about 46% of all Iberian newborns. Data reveals that Iberia has one of the highest FAOD prevalence in Europe (1:7,914) and that Portugal has the highest birth prevalence of FAOD reported so far (1:6,351), strongly influenced by the high prevalence of medium-chain acyl-CoA dehydrogenase deficiency (MCADD; 1:8,380), one of the highest ever reported. This is justified by the fact that more than 90% of Portuguese MCADD patients are of Gypsy origin, a community characterized by a high degree of consanguinity. From the comparative analysis of various populations with comparable data other differences emerge, which points to the existence of significant variations in FAOD prevalences among different populations, but without any clear European variation pattern. Considering that FAOD are one of the justifications for MS/MS NBS, the now estimated birth prevalences stress the need to screen all Iberian newborns for this group of inherited metabolic disorders.

Serum vitamin B12 levels during the first trimester of pregnancy correlate with newborn screening markers of vitamin B12 deficiency.

INTRODUCTION: Low maternal vitamin B12 status is a risk factor for various adverse pregnancy outcomes. Although vitamin B12 deficiency is not a primary target of newborn screening (NBS) programs, measurements of propionylcarnitine (C3) and its ratios with acetylcarnitine (C3/C2) and palmitoylcarnitine (C3/C16) may incidentally identify vitamin B12-deficient newborns. The objective of this study was to measure vitamin B12 levels in women during the first trimester of pregnancy, evaluate predictors of these concentrations, and study their relationship with newborn screening results. DESIGN: Vitamin B12 concentrations were evaluated in 204 women during the first trimester of pregnancy and possible confounding factors were analyzed. After giving birth, data of their newborns (189) were collected (sex, gestational age, birthweight) and the acylcarnitine profile obtained by tandem mass spectrometry during NBS was analyzed. To assess the effects of the variables on vitamin B12 serum concentrations and newborn screening markers, stepwise multiple linear regression models were used. RESULTS: The mean serum concentration of vitamin B12 was 370.8 pmol/L (502.4 pg/mL) (SD 142.81). Vitamin B12 concentrations were significantly lower in smokers (p=0.027), and in women with low meat consumption (p=0.040). There was a significant inverse correlation between mothers'’ vitamin B12 concentrations and their children’'s C3 (r=-0.24; p=0.001), C3/C2 (r=-0.23; p=0.002) and C3/C16 levels (r=-0.20; p=0.006). CONCLUSIONS: Newborn screening markers (C3, C3/C2, and C3/C16) present an inverse correlation with maternal vitamin B12 status in the first trimester of pregnancy. Regarding factors that may influence maternal serum vitamin B12 levels during the first trimester, smoking seems to have a negative effect, and meat consumption a positive effect.

Neonatal carnitine palmitoyltransferase II deficiency associated with Dandy-Walker syndrome and sudden death.

Neonatal onset of carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive, often lethal disorder of the mitochondrial beta-oxidation of long-chain fatty acids. It is a rare multiorgan disease which includes hypoketotic hypoglycemia, severe hepatomuscular symptoms, cardiac abnormalities, seizures and lethargy, as well as dysmorphic features. Until now, only 22 affected families have been described in the literature. An increasing number of mutations are being identified in the CPT2 gene, with a distinct genotype-phenotype correlation in most cases. Herein we report a new case of neonatal CPT II deficiency associated with Dandy-Walker syndrome and sudden death at 13 days of life. CPT II deficiency was suggested by acylcarnitine analysis of dried-blood on filter paper in the expanded newborn screening. Genetic analysis of the CPT2 gene identified the presence of a previously described mutation in homozygosity (c.534_558del25bpinsT). All lethal neonatal CPT II deficiency patients previously described presented severe symptoms during the first week of life, although this was not the case in our patient, who remained stable and without apparent vital risk during the first 11 days of life. The introduction of tandem mass spectrometry to newborn screening has substantially improved our ability to detect metabolic diseases in the newborn period. This case illustrates the value of expanded newborn screening in a neonate with an unusual clinical presentation, combining hydrocephalus and sudden death, that might not commonly lead to the suspicion of an inborn error of metabolism.