Advancing Neonatal Screening for Pyridoxine-Dependent Epilepsy-ALDH7A1 Through Combined Analysis of 2-OPP, 6-Oxo-Pipecolate and Pipecolate in a Butylated FIA-MS/MS Workflow.

Pyridoxine-dependent epilepsy (PDE) represents a group of rare developmental and epileptic encephalopathies. The most common PDE is caused by biallelic pathogenic variants in (PDE-ALDH7A1; OMIM #266100), which encodes α-aminoadipate semialdehyde (α-AASA) dehydrogenase, a key enzyme in lysine catabolism. Affected individuals present with seizures unresponsive to conventional anticonvulsant medications but responsive to high-dose of pyridoxine (vitamin B6).

Diagnostic performance of morphological analysis and red blood cell parameter-based algorithms in the routine laboratory screening of heterozygous haemoglobinopathies.

Objectives: The aim of this study was to carry out a cross-analysis of the morphological abnormalities (MA) and the electrophoretic profile (EP) of blood samples suspect for heterozygous haemoglobinopathies (HTZ HGP). Screening for HTZ HGP was based on erythrocyte parameters provided by the Sysmex XN analysers.

Methods: A total of 596,000 blood samples was included in the study.

Data-driven consideration of genetic disorders for global genomic newborn screening programs.

Purpose: Over 30 international studies are exploring newborn sequencing (NBSeq) to expand the range of genetic disorders included in newborn screening. Substantial variability in gene selection across programs exists, highlighting the need for a systematic approach to prioritize genes.

Methods: We assembled a data set comprising 25 characteristics about each of the 4390 genes included in 27 NBSeq programs.

Unravelling Faecal Microbiota Variations in Equine Atypical Myopathy: Correlation with Blood Markers and Contribution of Microbiome.

Hypoglycin A and methylenecyclopropylglycine are protoxins responsible for atypical myopathy in equids. These protoxins are converted into toxins that inhibit fatty acid -oxidation, leading to blood accumulation of acylcarnitines and toxin conjugates, such as methylenecyclopropylacetyl-carnitine. The enzymes involved in this activation are also present in some prokaryotic cells, raising questions about the potential role of intestinal microbiota in the development of intoxication.

Population-based, first-tier genomic newborn screening in the maternity ward.

The rapid development of therapies for severe and rare genetic conditions underlines the need to incorporate first-tier genetic testing into newborn screening (NBS) programs. A workflow was developed to screen newborns for 165 treatable pediatric disorders by deep sequencing of regions of interest in 405 genes. The prospective observational BabyDetect pilot project was launched in September 2022 in a maternity ward of a public hospital in the Liege area, Belgium.

[Neonatal screening for cystic fibrosis in the Liège region : first evaluation after 4 years].

Since January 2020, neonatal screening for cystic fibrosis (CF-NBS) has been implemented in the Wallonia-Brussels Federation. It's based on the immunoreactive trypsin (IRT1) assay between day 2 and day 4, associated with a 12 CFTR pathogenic variants analysis and with an IRT control on day 21. The aim of this study is to evaluate the performance of our CF-NBS in Liège according to the quality criteria defined by the European Cystic Fibrosis Society's working group on neonatal screening.

Data-driven consideration of genetic disorders for global genomic newborn screening programs.

Purpose: Over 30 international studies are exploring newborn sequencing (NBSeq) to expand the range of genetic disorders included in newborn screening. Substantial variability in gene selection across programs exists, highlighting the need for a systematic approach to prioritize genes.

Methods: We assembled a dataset comprising 25 characteristics about each of the 4,390 genes included in 27 NBSeq programs.

New Pathophysiological Insights from Serum Proteome Profiling in Equine Atypical Myopathy.

Equine atypical myopathy (AM) is a severe environmental intoxication linked to the ingestion of protoxins contained in seeds and seedlings of the sycamore maple () in Europe. The toxic metabolites cause a frequently fatal rhabdomyolysis syndrome in grazing horses. Since these toxic metabolites can also be present in cograzing horses, it is still unclear as to why, in a similar environmental context, some horses show signs of AM, whereas others remain clinically healthy.

Untargeted Metabolomics Profiling Reveals Exercise Intensity-Dependent Alterations in Thoroughbred Racehorses' Plasma after Routine Conditioning Sessions.

Thoroughbred (TB) racehorses undergo rigorous conditioning programs to optimize their physical and mental capabilities through varied exercise sessions. While conventional investigations focus on limited hematological and biochemical parameters, this field study employed untargeted metabolomics to comprehensively assess metabolic responses triggered by exercise sessions routinely used in TB conditioning. Blood samples were collected pre- and post-exercise from ten racehorses, divided into two groups based on exercise intensity: high intensity ( = 6, gallop at ± 13.

Mid-Term Evolution of the Serum Acylcarnitine Profile in Critically Ill Survivors: A Metabolic Insight into Survivorship.

It is unknown if the abnormal acylcarnitine (AC) profile observed early after discharge of a prolonged stay in an intensive care unit (ICU) would persist over time. This prospective observational study aimed to describe the mid-term AC profile evolution in survivors of a prolonged ICU stay (≥7 days). Adults enrolled in our post-ICU follow-up program and who attended the consultation 3 months (M3) after discharge were included.

Tissue Specific Distribution and Activation of Toxins in Horses Suffering from Atypical Myopathy.

Equine atypical myopathy is caused by hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG), the known protoxins of sycamore maple (). Various tissues from five atypical myopathy cases were analyzed but only HGA was found. Whether deamination of MCPrG has already occurred in the intestine as the first stage of metabolization has not been investigated.

Serum Acylcarnitines Profile in Critically Ill Survivors According to Illness Severity and ICU Length of Stay: An Observational Study.

The acylcarnitine (AC) profile has been shown to be altered in survivors of a prolonged stay in intensive care unit (ICU), with higher short-chain derivates compared to reference ranges. The present study aimed at describing the AC profile of patients surviving a short ICU stay versus patients surviving a >7-day multiple organ dysfunction. Patients discharged from ICU after an elective and non-complicated cardiac surgery (CS) were recruited.

Newborn screening for sickle cell disease in Kisangani, Democratic Republic of the Congo: an update.

Background: Neonatal screening is the first action necessary to identify children with sickle cell disease (SCD) and thus ensure their care. Using rapid tests to give an immediate result to families is a new resilient approach of great interest. These two aspects are essential for establishing an adequate health policy for this disease.

Moroccan Experience of Targeted Screening for Inborn Errors of Metabolism by Tandem Mass Spectrometry.

Background: Expanded newborn screening using tandem mass spectrometry (MS/MS) for inborn errors of metabolism (IEM), such as organic acidemias (OAs), fatty acid oxidation disorders (FAODs), and amino acid disorders (AAs), is increasingly popular but has not yet been introduced in Africa. With this study, we aim to establish the disease spectrum and frequency of inborn errors of OAs, FAODs, and AAs in Morocco.

Methods: Selective screening was performed among infants and children suspected to be affected with IEM between 2016 and 2021.

Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours.

Rapid Whole Genome Sequencing (rWGS) represents a valuable exploration in critically ill pediatric patients. Early diagnosis allows care to be adjusted. We evaluated the feasibility, turnaround time (TAT), yield, and utility of rWGS in Belgium.

BCKDK deficiency: a treatable neurodevelopmental disease amenable to newborn screening.

There are few causes of treatable neurodevelopmental diseases described to date. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder characterized by autism, intellectual disability and microcephaly. We report the largest cohort of patients studied, broadening the phenotypic and genotypic spectrum.

Pairing parents and offspring's HemoTypeSC Test to validate results and confirm sickle cell pedigree: a case study in Kisangani, the Democratic Republic of the Congo.

Objectives: HemoTypeSC is one of the immunoassay methods currently used for the early diagnosis of Sickle Cell Disease (SCD) in newborns. Earlier diagnosis remains the key strategy for early preventive care needs and parents' education about the child's future well-being throughout his life. Before considering these children as sick and aligning them for regular medical monitoring, it may be valuable to confirm the HemoTypeSC result with a secondary laboratory testing method.

: A Potential Risk of Poisoning for Several Herbivore Species.

is a worldwide-distributed tree which contains toxins, among them hypoglycin A (HGA). This toxin is known to be responsible for poisoning in various species, including humans, equids, Père David's deer and two-humped camels. We hypothesized that any herbivore pasturing with in their vicinity may be at risk for HGA poisoning.

Financial cost and quality of life of patients with spinal muscular atrophy identified by symptoms or newborn screening.

Aim: To compare the societal financial costs and quality of life (QoL) of untreated patients with spinal muscular atrophy (SMA) and treated patients identified because they presented symptoms or were identified by early testing (sibling or newborn screening).

Method: Data from two different sources were used: data collected prospectively in untreated patients from 2016 to 2018 and data collected during a prospective follow-up study from 2018 to 2021. Patients or their caregiver completed a questionnaire that included questions on direct medical and non-medical costs, indirect non-medical costs, and health-related QoL.

Altered Serum Acylcarnitines Profile after a Prolonged Stay in Intensive Care.

A stay in intensive care unit (ICU) exposes patients to a risk of carnitine deficiency. Moreover, acylated derivates of carnitine (acylcarnitines, AC) are biomarkers for metabolic mitochondrial dysfunction that have been linked to post-ICU disorders. This study aimed to describe the AC profile of survivors of a prolonged ICU stay (≥7 days).