Inosine Pranobex (IP) - possibilities of its use in the treatment of COVID19

The finding that enzymes of purine metabolism interfere to the regulation of immune events is known from the findings of Giblett, et al. [1], that Adenosine Deaminase (ADA) deficiency leads to Severe Combined Immunbodeficiency (SCID), The same author described in 1975 case of&nbsp; T-immune deficiency caused by a deficiency of another purine metabolism enzyme - Purine Nucleoside Phosphorylase (PNP). Subsequently, otherl authors have described cases of hypo to agammaglobulinemia with 5´-nucleotidase (5-NT) deficiency in adults [2] and children [3].</p

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