In 2023, the Russian Federation expanded its national newborn screening (NBS) program from 5 to 36 conditions, 29 of which are inherited metabolic diseases (IMDs). This study presents the first nationwide results and outcomes of the expanded NBS program. Between January 2023 and December 2024, dried blood spots from 2,466,615 newborns (98.53% of the birth cohort) were analyzed for IMDs using MS/MS. Screen-positive cases were referred to the national reference center for confirmatory testing, which included biochemical (MS/MS and GC-MS) and genetic analyses (NGS). A total of 41,728 neonates (1.69%) screened positive, of whom 37,733 underwent confirmatory testing. It resulted in 834 confirmed diagnoses of IMDs (1 in 2900 live births). Phenylketonuria was the most prevalent IMD (n = 538; 1 in 4600), followed by MCADD (n = 99; 1 in 25,000). Distinct regional and ethnic variations were observed, including a high prevalence of tyrosinemia type 1 in the Chechen Republic and MCADD in North Ossetia. The integration of NGS was essential for resolving complex cases, such as identifying heterozygous carriers and dual diagnoses. These findings underscore the program’s clinical utility, highlight unique epidemiological patterns, and identify challenges such as false positives and diagnostic complexities, which will guide future refinements.

A fifth world case of autosomal recessive Siddiqi syndrome (SIDDIS) related to FITM2 gene is presented. In a consanguineous Lezgin (a Dagestan ethnicity) family, there were two affected brothers aged 28 yrs (proband, personally examined) and 32 yrs. Whole-exome sequencing followed by familial Sanger sequencing detected a novel FITM2 missence variant c.452A>G, p.Asp151Gly homozygous in both patients and heterozygous in parents and unaffected brother. SIDDIS typical features in the patients were physical and motor delay with neuropsychiatric regress, loss of speech and walking, early-onset progressive sensorineural deafness, cognitive deficiency, skin lesion. However, there was no dystonia, which is a characteristic SIDDIS feature, while at least the proband had spastic paraparesis not described in SIDDIS earlier. Another distinction was mental state: behavioral disorders in both patients, positive symptoms in the proband and severe cognitive impairment in the brother. The case expands our understanding of the clinical and molecular-genetic spectrum of SIDDIS.

Scientific relevance. Medication adherence is an important condition for effective and safe treatment. The adherence of patients to prescriptions is tracked by assessing their condition, counting the pills taken, and using other indirect methods. Digital technologies can help healthcare providers improve their patients’ medication adherence.Aim. The authors aimed to review literature describing the medication adherence impact on treatment effectiveness, as well as digital solutions accompanying pharmacotherapy.Discussion. Poor adherence to treatment is a significant risk factor for patients. The most common examples of poor adherence are omissions and delays in the timing of doses. Compared with classical daily dosing, individualised regimens significantly increase the risk of adherence errors. Significant consequences of non-adherence include exacerbation of the disease, insufficient effectiveness of treatment, adverse drug reactions, and drug resistance. Promising hardware and software approaches to supporting medication adherence include innovative technological solutions (pillboxes, bottles with electronic reminder systems, digital pills, and smart medication adherence monitoring systems), mobile apps, and chatbots.Conclusions. Digital solutions to support pharmacotherapy help improve patients’ adherence to their dosing regimens and individualise their treatment. Further research is needed to select the most promising areas and develop novel digital technologies.

The DNAAF11 gene, also known as LRRC6 , follows autosomal recessive inheritance and plays a key role in the assembly of dynein, a protein necessary for the normal functioning of cilia. Mutations in this gene can lead to primary ciliary dyskinesia (PCD), a rare hereditary disease characterized by impaired function of the ciliated epithelium, primarily in the respiratory system but also in other organs. Defects in dynein arms associated with mutations in the DNAAF11 gene disrupt their rhythmic movement, leading to mucus stagnation, chronic inflammatory processes, and increased susceptibility to respiratory tract infections. The aim of this work is to describe the clinical case of a family consisting of a mother and her son, both with a confirmed diagnosis of PCD. The study revealed a mutation in the DNAAF11 gene in both patients: the mother’s was in a homozygous state (NM_012472.6: c.436G>C), and her son’s was in a compound heterozygous state: one NM_012472.6: c.436G>C variant inherited from the mother (not previously described), and the second, NM_012472.6: c.1011A>G, inherited from the father. The child’s diagnosis was confirmed by segregation analysis. Methods. The PCD diagnosis included: molecular genetic analysis, segregation analysis, video microscopy, electron microscopy of the ciliated epithelium, air-liquid interface (ALI) cell culture, and immunofluorescence staining. Conclusion. This clinical case highlights the importance of identifying genetic relationships and features of PCD within families. The newly discovered mutations expand the spectrum of variants in the DNAAF11 gene associated with ciliary defects in PCD and emphasize the need for molecular genetic studies. Early diagnosis contributes to timely treatment initiation, preventing disease progression and improving patients’ quality of life.

Mass screening of newborns for 36 hereditary diseases in the Russian Federation will enable the reduction of childhood disability and mortality from hereditary disorders, as well as the identification of all-Russian and regional population-genetic features of the screened disorders. The study aimed to assess the results of newborn screening (NBS), including expanded newborn screening (ENBS), in the Republic of North Ossetia-Alania obtained between January 1, 2023, and December 31, 2024, as well as to study clinical and population-genetic characteristics of the diseases screened in the region. In phase I of assessment, biochemical testing, tandem mass spectrometry, and DNA diagnostics were performed, and the TREС/KREС levels were determined in 14,994 newborns. In 355 cases (2.36%), positive values were revealed. In phase II, the necessary laboratory and subsequent confirmatory DNA diagnostics were carried out in 324 cases (91.2%): repeated analysis by MS/MS and DNA diagnostics (for hereditary metabolic diseases), immunophenotyping (for primary immunodeficiency states). During the 2-year study, a total of 37 diagnoses were established, which accounted for 0.25% of all children screened in phase I and clearly indicated the program's success and effectiveness. We managed to verify the specific spectrum of mutations characteristic of phenylketonuria (PKU) and medium-chain fatty acid acyl-CoA dehydrogenase deficiency (MCADD). The frequency of the disorder assessed within the framework of newborn screening was determined. The frequency of all PKU forms was 1 : 1153 newborns, and the frequency of MCADD was 1 : 789 newborns surveyed. All children are listed as sick in the medical genetic consultation of the Republic of North Ossetia-Alania; they receive treatment in accordance with the clinical guidelines.

Since January 2023, the Russian Federation has implemented expanded neonatal screening for 36 hereditary disorders, which has changed the diagnostic algorithm for hyperphenylalaninemia/phenylketonuria (HPA/PKU) by introducing tandem mass spectrometry (MS/MS) on the second day of life, followed by confirmatory biochemical and molecular testing in newborns at risk. We analyzed 1247 newborns aged 5–15 days with elevated phenylalanine levels (≥120 µmol/L) and a phenylalanine to tyrosine ratio of at least 1 detected during the first stage of screening using MS/MS. At the reference center, newborns underwent repeat biochemical testing and stepwise molecular analysis of HPA-associated genes. Two pathogenic variants in HPA-associated genes were identified in 538 newborns, including 534 newborns with biallelic pathogenic variants in PAH and 4 with BH4-deficient forms (PTS, QDPR). The incidence of molecularly confirmed HPA was 1:4518 newborns (95% CI: 1:4152–1:4925). The PAH variant spectrum was dominated by p.Arg408Trp (c.1222C>T) (33.4%). Genotype-based analysis indicated that 73 newborns (13.7%) were likely responsive to cofactor therapy, whereas 222 (41.6%) were potentially responsive. These findings define the molecular epidemiology of HPA in Russia and support early genetic stratification for diagnosis and treatment.