The First Results of Extended Newborn Screening in Slovakia—Differences between the Majority and the Roma Ethnic Group

The authors present the first results of the National Extended Newborn Screening (ENS) in Slovakia in the majority (M) and the Roma (R) ethnic populations. A follow-up of ethnicity has been introduced in newborn screening for cystic fibrosis (NSCF) and afterwards to the entire ENS program comprising of 23 inborn errors of metabolism (IEM). In 2013–2015, a total of 165,648 newborns were investigated in ENS, 23,321 of them (14%) were the R ethnic group, a total of 313 positive cases were discovered (total ENS prevalence = 1:529, M = 1:758, R = 1:198). In the R ethnic group, there was a slightly higher prevalence of congenital hypothyroidism (CH), only one case of CF, and no cases of congenital adrenal hyperplasia (CAH) in the R ethnic group. The ENS prevalence of IEM detected by MS/MS was significantly higher in the R ethnic group than in M group (M = 1:1670 vs. R = 1:234, OR:7,13). Significant differences in the prevalence of individual types of IEM were also found. While PKU and other aminoaciduria and organic acidurias dominate in the M group, the fatty acid oxidation disorders (MCAD, SCAD) and carnitine defects (CUD) were more frequent in the R newborn group. Despite the preliminary nature of the results, an ethnic approach to ENS enables the recording of the ethnic differences in the screen prevalence of individual disorders, which would not be apparent without this approach

An unusually high frequency of SCAD deficiency caused by two pathogenic variants in the ACADS gene and its relationship to the ethnic structure in Slovakia

Abstract Background Short-chain acyl-CoA dehydrogenase deficiency (SCADD) represents a rare autosomal recessive inborn metabolic disorder of mitochondrial β-oxidation of monocarboxylic acids. Clinical symptoms can vary from a severe life-threatening condition to an asymptomatic state, reported in the majority of cases. Since the expansion of newborn screenings, more than three hundred probands were admitted for molecular-genetic analysis, most selected because of elevated values of C4-acylcarnitine detected in newborn screenings in Slovakia. Searching for the principal genomic changes led us to the selection of sixty-two patients in whom the presence of sequence variants in the ACADS gene was analysed and correlated with the available biochemical and clinical data. Methods Biochemical and molecular genetic tests were performed. Acylcarnitine profiles focused on an elevated level of C4-acylcarnitine, which was analysed via tandem mass spectrometry. Urinary organic acids, specifically a quantity of ethylmalonic acid, were determined by gas chromatography/mass spectrometry. The entire coding region of the ACADS gene was sequenced. A low-cost restriction fragment length polymorphism of PCR amplified fragments analysis (PCR-RFLP) of pathogenic variants was introduced and implemented for the molecular-genetic algorithm appropriate for the Slovak population. Results Our molecular genetic study was performed on sixty-two patients with a pathological biochemical pattern related to short-chain acyl-CoA dehydrogenase deficiency. In this cohort, we discovered a high occurrence of two rare pathogenic variants—the deletion c.310_312delGAG and the substitution c.1138C>T, with allelic frequencies of 64% and 31%, respectively. Up to 86% of investigated individuals belong to the Roma ethnic group. Conclusions Analogous to other countries, SCADD is not included in the newborn screening programme. Based on the exceeded levels of the specific biomarker C4-acylcarnitine as well as ethylmalonic acid, we revealed a high prevalence of short-chain acyl-CoA dehydrogenase deficiency cases, confirmed by the findings of two rare pathogenic variants. A deletion c.310_312delGAG and c.1138C > T substitution in the ACADS gene appear with a high frequency in the Roma ethnic group of Slovakia. Due to the uncertainty of the pathogenicity and clinical consequences, it is important to follow up the morbidity and mortality in these patients over time and evaluate SCADD in relation to clinical outcomes and preventive healthcare recommendations

Regulatory landscape of providing information on newborn screening to parents across Europe

Newborn screening (NBS) is an important part of public healthcare systems in many countries. The provision of information to parents about NBS is now recognised as an integral part of the screening process. Informing parents on all aspects of screening helps to achieve the benefits, promote trust and foster support for NBS. Therefore, policies and guidelines should exist to govern how the information about NBS is provided to parents, taking into account evidence-based best practices. The purpose of our survey was to explore whether any legally binding provisions, guidelines or recommendations existed pertaining to the provision of information about NBS to parents across Europe. Questions were designed to determine the regulatory process of when, by whom and how parents should be informed about screening. Twenty-seven countries participated in the survey. The results indicated that most countries had some sort of legal framework or guidelines for the provision of information to parents. However, only 37% indicated that the provision of information was required prenatally. The majority of countries were verbally informing parents with the aid of written materials postnatally, just prior to sample collection. Information was provided by a neonatologist, midwife or nurse. A website dedicated to NBS was available for 67% of countries and 89% had written materials about NBS for parents. The survey showed that there is a lack of harmonisation among European countries in the provision of information about NBS and emphasised the need for more comprehensive guidelines at the European level.Institutional support was provided by projects LM2018132 from the Large Infrastructure Projects of the Czech Ministry of Education, PROGRES Q26 from Charles University and RVO VFN 64165 from the Ministry of Health, Czech Republic. Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN)—Project ID No. 739543.info:eu-repo/semantics/publishedVersio

Global impact of COVID-19 on newborn screening programmes

Introduction The global COVID-19 pandemic has presented extraordinary disruption to healthcare services and exposed them to numerous challenges. Newborn screening (NBS) programmes were also affected; however, scarce data exist on the impact of COVID-19 on NBS. Methods We conducted an international survey to assess the global impact of COVID-19 on NBS, with the main aim of gathering the experiences of the COVID-19 pandemic from a large and representative number of NBS centres worldwide. Results The results of our study showed that COVID-19 impacted the NBS programmes, at least partially, in 29 out of 38 responding countries. Majority of the screening centres experienced a broad spectrum of difficulties and most were affected more in the second wave of the pandemic. Delays and unreliability with the postal service as well as flight cancellations caused delays in samples arriving to screening centres and with the provision of laboratory equipment and reagents. The availability of laboratory staff was sometimes reduced due to infection, quarantine or reassignment within the healthcare facility. Sample collection at home, second-tier tests and follow-up were also affected. Social restrictions and interruptions in public transport added to these difficulties. Only a limited number of centres managed to retain a fully functioning NBS programme. Conclusion As the pandemic might continue or could recur in future years, it would be useful to develop guidelines to protect these valuable services