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The 2021-updated guidelines of the Spanish Society of Neonatology Guidelines have moved the zone of parental discretion to 23 + 0-23 + 6 weeks. The objective of this study was to describe the changes in perinatal management at this gestational age along the last decade and to determine if a more active perinatal management has contributed to improved outcomes.Retrospective analysis of prospectively collected data from the 23-week infants included in the Spanish SEN 1500 neonatal network during the period 2010-2019. The main study outcomes were survival at discharge and survival without major morbidity of actively managed infants. Two periods were compared: 2010-2014 (Period 1) and 2015-2019 (Period 2). NICUs were classified into low activity NICUs (less than 50 admissions of very low birth weight infants per year) and high activity NICUs (50 or more admissions).A total of 381 infants were included, 182 in Period 1 and 199 in Period 2. In Period 2 an increase in the use of intrapartum magnesium sulfate (21.5% vs 39.9%,A change to a more active intention to treat infants born at 23 weeks is taking place in Spain. But the survival rate of the actively-managed infants has remained stable around 25-30% during the study period. A multidisciplinary effort is needed to improve outcomes in this population.

PURPOSE: Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype. METHODS: Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020. RESULTS: Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial. CONCLUSION: The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed. ispartof: GENETICS IN MEDICINE vol:23 issue:1 pages:202-210 ispartof: location:United States status: published

The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging. Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%). Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II. Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4). Overall, 27 variants were identified, 12 of which are novel. The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.

Energy deficiency is a cause for myocardial dysfunction during septic shock. In rodents, septic shock decreases the oxidation of long-chain fatty acids and glucose in the myocardium causing energy deficiency. However, the effect of septic shock on myocardial energy metabolites in large animals and human is unknown. Investigate the effects of septic shock on myocardial energy metabolites in domestic pigs. Seventeen female pigs divided into control and lipopolysaccharide (LPS)-induced septic shock groups. Myocardial metabolites were analyzed ex vivo by 1H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. Gene and protein expression analysis were analyzed by real-time PCR and western blot. Septic shock was associated with an increase in myocardial levels of short- and medium-chain acylcarnitines, lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression. COX-2 and prostaglandin E4 receptor gene expression also increased in the septic myocardium, although the only elevated eicosanoid in the septic animals was thromboxane B2. Myocardial levels of niacin, taurine, glutamate, glutamine, and glutathione were higher, and hypoxanthine levels lower in septic pigs than controls. In pigs, septic shock induced by LPS caused myocardial changes directed to decrease the oxidation of medium- and short-chain fatty acid without an effect on long-chain fatty acid oxidation. The increase in myocardial levels of lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression suggest that septic shock decreases pyruvate dehydrogenase complex activity and glucose oxidation. Homeostasis of niacin, taurine, glutamate, glutamine, glutathione, hypoxanthine and thromboxane B2 is also affected in the septic myocardium.

The transition process from paediatric to adult care is a subject of great interest in recent years, especially in chronic diseases with childhood onset, such as inborn errors of metabolism (IEM). Advances in diagnosis and treatment of these diseases have improved their prognosis, with a high number of patients with IEM who currently reach adult age and need to be attended to by non-paediatric professionals. The objective of this work is to establish action guidelines so that the specialists involved can guarantee a successful transition of these patients' healthcare.After carrying out a bibliographic review of the subject, the authors, beginning with their own experience, produced an initial document which was subjected to successive debates until the final document was obtained. The consensus recommendation was decided by the majority in case of criterion discrepancy.A series of recommendations are presented for the best clinical management of the transitions of care of patients with IEM from the paediatric to adult care setting in order to achieve the best results in this process given the special characteristics of this patient subgroup and the main difficulties entailed in the transition process.The role of the internal medicine doctor in this transition process and correct interrelation with the paediatric and social setting is stressed. Furthermore, actions and attitudes are suggested to improve the quality of said transition.

RATIONALE Rapid and specific screening methods to detect abnormal metabolites in biological fluids are important for the diagnosis of many Inborn Errors of Metabolism (IEM). In Galicia (N.W. Spain), where newborn screening (NBS) has long used both blood and urine dried samples, an expanded NBS by tandem mass spectrometry (MS/MS) begun in July 2000 analyzing amino acids and acylcarnitines in blood. The purpose of this study is the development of methods to widen and to complement the present NBS with the study of the selected metabolites in urine. METHODS We studied and optimized the fragmentation of a total of 96 marking compounds of IEM, as well as 34 isotopically labeled internal standards (IS). The isobaric interferences were resolved with the use of alternative fragmentation in 14 of the 28 groups found. The methods were validated for 68 compounds following the recommendations of the NCCLS. RESULTS We have developed electrospray ionization (ESI)- MS/MS methods in positive and negative ionization modes to detect selected metabolites in urine. The study was performed by direct injection of amino acids and acylcarnitines in positive mode, and organic acids, acylglycines, purines and pyrimidines in negative mode. Run times were 2.5 and 2.6 min, respectively, allowing the daily analysis of a high number of samples. CONCLUSIONS The validated methods were proved effective for the simultaneous study of a large number of metabolites which are commonly present in urine samples and are used for detecting IEM. The evaluation was done by searching diagnostic profiles with multiple markers to increase sensitivity and specificity (e.g., acylcarnitines plus amino acids) or with specific urine markers (cystine, homogentisic acid, sialic acid, N-acetylaspartic acid, etc.). Copyright © 2012 John Wiley & Sons, Ltd.

Background and objective The transition process from paediatric to adult care is a subject of great interest in recent years, especially in chronic diseases with childhood onset, such as inborn errors of metabolism (IEM). Advances in diagnosis and treatment of these diseases have improved their prognosis, with a high number of patients with IEM who currently reach adult age and need to be attended to by non-paediatric professionals. The objective of this work is to establish action guidelines so that the specialists involved can guarantee a successful transition of these patients’ healthcare. Methodology After carrying out a bibliographic review of the subject, the authors, beginning with their own experience, produced an initial document which was subjected to successive debates until the final document was obtained. The consensus recommendation was decided by the majority in case of criterion discrepancy. Results A series of recommendations are presented for the best clinical management of the transitions of care of patients with IEM from the paediatric to adult care setting in order to achieve the best results in this process given the special characteristics of this patient subgroup and the main difficulties entailed in the transition process. Conclusions The role of the internal medicine doctor in this transition process and correct interrelation with the paediatric and social setting is stressed. Furthermore, actions and attitudes are suggested to improve the quality of said transition.

Resumen Antecedentes y objetivo El proceso de transicion de la asistencia pediatrica a la adulta es un tema de gran interes en los ultimos anos, especialmente en enfermedades cronicas de inicio en la infancia, como los errores congenitos del metabolismo (ECM). Los avances en el diagnostico y el tratamiento de estas enfermedades han mejorado su pronostico, encontrando en la actualidad un elevado numero de pacientes con ECM que alcanzan la edad adulta y necesitan ser atendidos por profesionales no pediatricos. El objetivo de este trabajo es establecer unas pautas de actuacion para que los especialistas involucrados garanticen una transicion exitosa de la atencion sanitaria de estos pacientes. Metodologia Tras realizar una revision bibliografica del tema, los autores, partiendo de su propia experiencia, elaboraron un documento inicial que fue sometido a sucesivos debates hasta obtener el documento definitivo. En caso de discrepancia de criterio, la recomendacion de consenso se decidio por mayoria. Resultados Se presentan una serie de recomendaciones para el mejor abordaje clinico de la transicion asistencial de los pacientes con ECM desde el entorno pediatrico a la asistencia de adultos, con el objetivo de conseguir los mejores resultados en este proceso, dadas las caracteristicas especiales de este subgrupo de pacientes, asi como las principales dificultades que conlleva el proceso de transicion. Conclusiones Se resalta el papel del medico internista en este proceso de transicion y su correcta articulacion con el entorno pediatrico y social. Asimismo, se recomiendan acciones y actitudes para mejorar la calidad de dicha transicion.

Resumen: Objetivos: Conocer la prevalencia en España de los diferentes errores congénitos del metabolismo que presentan homocistinuria y establecer las medidas oportunas para garantizar su prevención, diagnóstico y tratamiento, en aquellos casos posibles. Material y métodos: En abril 2009 se realizó una encuesta nacional de carácter transversal mediante cuestionario enviado a 35 centros, en los que se atiende a pacientes infantiles y adultos. La finalidad de la encuesta era establecer la prevalencia en ese momento recogiendo el histórico de pacientes que cada centro tuviera documentados. Resultados: A través de los cuestionarios respondidos por 25 médicos de 16 centros, se han identificado 75 pacientes: 41 defectos de transulfuración (uno fallecido), 27 de remetilación (6 fallecidos) y 7 sin diagnóstico etiológico definitivo. La edad de diagnóstico muestra una amplia variación, en 18 casos había más de un hermano afectado. Las manifestaciones clínicas más graves inciden en el grupo de los pacientes afectados de trastornos de la remetilación. Destaca el alto porcentaje de déficit cognitivo, seguido de la patología de cristalino; casi la mitad de los pacientes presentan trastornos neurológicos, es elevada la afectación vascular en los adultos con deficiencia de CBS; las opciones terapéuticas más utilizadas han sido el ácido fólico, la hidroxicobalamina y la betaína. Conclusiones: A la vista de estos resultados, y en especial del escaso número de deficiencias de CBS detectadas, se concluye la necesidad de implantar el cribado neonatal para la homocistinuria clásica y asegurar la puesta en marcha del proceso diagnóstico oportuno en todos los pacientes de riesgo. Abstract: Objectives: To determine the prevalence of homocystinuria in Spain and to establish the measures and mechanisms to ensure its prevention, diagnosis and treatment. Material and methods: A national cross-sectional survey was conducted by means of a questionnaire sent to 35 hospitals in which children and adult patients are treated. Results: Using the questionnaires submitted by 25 physicians from 16 centres, 75 patients were identified: 41 transsulphuration defects (one deceased), 27 remethylation (six deaths) and 7 without a syndromic diagnosis. The age at diagnosis varied widely, and 18 cases had more than one sibling affected. The more severe clinical manifestations involved the patients with remethylation defects. There was a high percentage of cognitive impairment, followed by lens diseases. Almost half of the patients had neurological disorders. There was increased vascular involvement in CBS-deficient adults. The therapeutic options most used were, folic acid, hydroxycobalamin and betaine. Conclusions: In view of these results and especially the small number of CBS deficiencies detected, we conclude that there is a need to introduce newborn screening for classical homocystinuria and ensure implementation of an appropriate diagnostic workup in all patients at risk.

We report a case of congenital hypothyroidism (CH) with neurological and respiratory alterations due to a heterozygotic c.374-1G > A mutation of TITF1/NKX2-1. The hypothyroidism was detected using a neonatal screening protocol in which the thyroid stimulating hormone (TSH) threshold is re-set each day on the basis of within-day variability and between-day variation. In this case, the threshold on the day of the initial analysis was 8.2 mIU/L, and the measured TSH level in heel-prick blood was 8.3 mIU/L. Conflict of interest:None declared.

To determine the prevalence of homocystinuria in Spain and to establish the measures and mechanisms to ensure its prevention, diagnosis and treatment.A national cross-sectional survey was conducted by means of a questionnaire sent to 35 hospitals in which children and adult patients are treated.Using the questionnaires submitted by 25 physicians from 16 centres, 75 patients were identified: 41 transsulphuration defects (one deceased), 27 remethylation (six deaths) and 7 without a syndromic diagnosis. The age at diagnosis varied widely, and 18 cases had more than one sibling affected. The more severe clinical manifestations involved the patients with remethylation defects. There was a high percentage of cognitive impairment, followed by lens diseases. Almost half of the patients had neurological disorders. There was increased vascular involvement in CBS-deficient adults. The therapeutic options most used were, folic acid, hydroxycobalamin and betaine.In view of these results and especially the small number of CBS deficiencies detected, we conclude that there is a need to introduce newborn screening for classical homocystinuria and ensure implementation of an appropriate diagnostic workup in all patients at risk.