1. International survey on Phenylketonuria newborn screeningDomen Trampuž, Peter C. J. I. Schielen, Rolf H. Zetterström, Maurizio Scarpa, François Feillet, Viktor Kožich, Trine Tangeraas, Ana Drole Torkar, Matej Mlinarič, Daša Perko, Žiga Iztok Remec, Barbka Repič-Lampret, Tadej Battelino, Urh Grošelj, 2025, izvirni znanstveni članek Povzetek: ewborn screening for Phenylketonuria enables early detection and timely treatment with a phenylalanine-restricted diet to prevent severe neurological impairment. Although effective and in use for 60 years, screening, diagnostic, and treatment practices still vary widely across countries and centers. To evaluate the Phenylketonuria newborn screening practices internationally, we designed a survey with questions focusing on the laboratory aspect of the screening system. We analyzed 24 completed surveys from 23 countries. Most participants used the same sampling age range of 48–72 h; they used tandem mass spectrometry and commercial non-derivatized kits to measure phenylalanine (Phe), and had non-negative cut-off values (COV) set mostly at 120 µmol/L of Phe. Participants mostly used genetic analysis of blood and detailed amino acid analysis from blood plasma as their confirmatory methods and set the COV for the initiation of dietary therapy at 360 µmol/L of Phe. There were striking differences in practice as well. While most participants reported a 48–72 h range for age at sampling, that range was overall quite diverse Screening COV varied as well. Additional screening parameters, e.g., the phenylalanine/tyrosine ratio were used by some participants to determine the screening result. Some participants included testing for tetrahydrobiopterin deficiency, or galactosemia in their diagnostic process. Results together showed that there is room to select a best practice from the many practices applied. Such a best practice of PKU-NBS parameters and post-screening parameters could then serve as a generally applicable guideline.
Ključne besede: phenylketonuria, newborn, neonatal, screening, international, survey, laboratory, methods, cut-off
Objavljeno v DiRROS: 04.12.2025; Ogledov: 15; Prenosov: 10
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2. Gene therapy of rare diseases as a milestone in medicine : overview of the field and report on initial experiences in SloveniaUrh Grošelj, Marko Kavčič, Ana Drole Torkar, Jan Kafol, Duško Lainšček, Roman Jerala, Matjaž Sever, Samo Zver, Gregor Serša, Maja Čemažar, Primož Strojan, Aleš Grošelj, Mojca Žerjav-Tanšek, Špela Miroševič, Simona Ivančan, Tomaž Prelog, David Gosar, Jasna Oražem, Matej Mlinarič, Sara Bertok, Jernej Kovač, Jana Kodrič, Saba Battelino, Marko Pokorn, Alojz Ihan, Janez Jazbec, Tadej Battelino, Damjan Osredkar, 2025, pregledni znanstveni članek Povzetek: Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients’ lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field since 2018, marked by successful gene therapy trials and treatments for various rare diseases. Significant strides have been made in the field of gene therapy in Slovenia, treating patients with spinal muscular atrophy and rare metabolic disorders, including the pioneering work on CTNNB1 syndrome. Additionally, immune gene therapy, exemplified by IL-12 adjuvant therapy for cancer, has been a focus of research in Slovenia. Through patient-centred initiatives and international collaborations, researchers in Slovenia are advancing preclinical research and clinical trials, paving the way for accessible gene therapies. Establishing clinical infrastructure and genomic diagnostics for rare diseases is crucial for gene therapy implementation. Efforts in this regard in Slovenia, including the establishment of a Centre for Rare Diseases, Centre for the Technologies of Gene and Cell Therapy, and rapid genomic diagnostics, demonstrate a commitment to comprehensive patient care. Despite the promises of gene therapy, challenges remain, including cost, distribution, efficacy, and long-term safety. Collaborative efforts are essential to address these challenges and ensure equitable access to innovative therapies for patients with rare diseases.
Ključne besede: gene therapy, rare genetic diseases, Slovenia, CAR-T cells, cancer, immune gene therapy
Objavljeno v DiRROS: 04.12.2025; Ogledov: 28; Prenosov: 12
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3. Postprandial time in tight range with faster insulin aspart compared with standard insulin aspart in youth with type 1 diabetes using automated insulin deliveryKlemen Dovč, Charles Spanbauer, Eleonora Chiarle, Nataša Bratina, Elke Fröhlich-Reiterer, Nejka Potočnik, Dessi P. Zaharieva, Tim Hropot, Maria Fritsch, Peter Calhoun, Tadej Battelino, 2025, izvirni znanstveni članek Povzetek: Aims The aim of this study was to assess postprandial glycaemic outcomes using automated insulin delivery with faster acting insulin aspart (FIA) or standard insulin aspart (SIA) over 4 weeks in youth (aged 10–18 years) with type 1 diabetes. Materials and Methods We undertook a secondary analysis of postprandial glycaemic outcomes from a double-blind, randomised, crossover study comparing FIA to SIA using an investigational version of MiniMed™ 780G. Endpoints included postprandial time in tight range (70–140 mg/dL; TITR), postprandial glucose excursions and peak glucose, and incremental area under curve (iAUC). Results The mean ± SD age of 30 included participants was 15.0 ± 1.7 years, 47% were male, mean HbA1c was 7.5% ± 0.9% (58 ± 9.8 mmol/mol) and the number of meals per day per participant was 3.2 ± 1.2 meals. Overall, the postprandial outcomes were improved with FIA compared with SIA. Mean glucose at the start of the meal was 151 mg/dL in the FIA group and reached a peak glucose of 194 mg/dL, compared with starting level of 151 mg/dL in the SIA group and a peak of 198 mg/dL (difference in excursion: −3.8 mg/dL; 95% confidence interval −5.8 to −1.7; p <0.001). FIA group also had a 1.9% increase in mean TITR (p = 0.02) and a 2.0-mg/dL decrease in mean iAUC (p = 0.003). Differences in outcomes were the most noticeable for breakfast, meals with a larger amount of carbohydrates (>45 g) and participants with lower insulin-to-carbohydrate ratios.Conclusions Faster insulin formulation with AID improved postprandial glycaemic outcomes and could be a useful therapeutical option in youth with type 1 diabetes that have challenges achieving glycaemic targets.
Ključne besede: postprandial time in tight, range standard insulin aspart in youth with type 1, automated insulin delivery
Objavljeno v DiRROS: 03.12.2025; Ogledov: 48; Prenosov: 17
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4. The role of the MTUS1 gene in the development of left ventricular noncompaction cardiomyopathy : a case reportTevž Gorjanc, Jaka Šikonja, Ana Drole Torkar, Mojca Žerjav-Tanšek, Jernej Kovač, Sara Bertok, Maruša Debeljak, Zvezdana Dolenc-Stražar, Marija Meznarič, Jernej Mlakar, Mirko Topalović, Gorazd Mlakar, Tadej Battelino, Urh Grošelj, 2025, drugi znanstveni članki Ključne besede: left ventricular noncompaction cardiomyopathy, microtubule-associated scaffold protein 1 (MTUS1), whole-genome sequencing
Objavljeno v DiRROS: 02.12.2025; Ogledov: 49; Prenosov: 24
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5. Integrating genetic insights, technological advancements, screening, and personalized pharmacological interventions in childhood obesityRobert Šket, Barbara Slapnik, Primož Kotnik, Klementina Črepinšek, Barbara Čugalj Kern, Tine Tesovnik, Barbara Jenko Bizjan, Blaž Vrhovšek, Žiga Iztok Remec, Maruša Debeljak, Tadej Battelino, Jernej Kovač, 2025, pregledni znanstveni članek Povzetek: Childhood obesity is a significant global health challenge with rising prevalence over the past 50 years, affecting both immediate and long-term health outcomes. The increase in prevalence from 0.7% to 5.6% in girls and 0.9% to 7.8% in boys highlights the urgency of addressing this epidemic. By 2025, it is estimated that 206 million children and adolescents aged 5–19 years will be living with obesity. This review explores the complex interplay of genomics and genetics in pediatric obesity, transitioning from monogenic and polygenic obesity to epigenetics, and incorporating advancements in omics technologies. The evolutionary purpose of adiposity, systemic evaluation of hyperphagia, and the role of various genetic factors are discussed. Technological advancements in genotyping offer new insights and interventions. The integration of genetic screening into clinical practice for early identification and personalized treatment strategies is emphasized.
Ključne besede: hemophilia, wearable, Florio HAEMO, adherence, patient satisfaction
Objavljeno v DiRROS: 27.11.2025; Ogledov: 105; Prenosov: 59
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6. Sex differences in cholesterol levels among prepubertal childrenJan Kafol, Mia Becker, Barbara Čugalj Kern, Jaka Šikonja, Matej Mlinarič, Katarina Sedej, Matej Kafol, Ana Drole Torkar, Jernej Kovač, Tadej Battelino, Urh Grošelj, 2025, izvirni znanstveni članek Povzetek: Background and aims: Sex differences in cholesterol levels are well documented in adults and adolescents, but limited data exist for prepubertal children. This study aimed to evaluate innate sex differences in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among prepubertal children, both in the general population and among those with familial hypercholesterolemia (FH). Methods: This cross-sectional study used data from Slovenia’s Universal FH Screening Program. Two populationbased random samples of children undergoing routine cholesterol screening at age 5 years were included from 2014 (N = 3412) and 2023 (N = 4182). In addition, a referred cohort from the Slovenian Hypercholesterolemia Registry (n = 1160, aged <10 years) who underwent genetic testing was analyzed. Results: In both the 2014 and 2023 cohorts, girls had significantly higher TC levels than boys (median difference: 0.10–0.11 mmol/L; p < 0.05). Among FH-negative children in the Registry, girls had on average 0.14 mmol/L higher TC and 0.13 mmol/L higher LDL-C than boys (both p < 0.05). No sex differences were observed in FHpositive children (p = 0.83 for TC; p = 0.82 for LDL-C). In the overall Registry cohort, after adjusting for FH status, girls had 0.11 mmol/L higher TC and 0.10 mmol/L higher LDL-C (both p < 0.05). Conclusion: Prepubertal girls have modestly higher TC and LDL-C than boys, a difference not observed in prepubertal FH-positive children, suggesting that the presence of a pathogenic FH variant may override innate physiological differences in lipid metabolism. These findings support universal early cholesterol screening and suggest that sex-specific reference values may improve early cardiovascular risk assessment in prepubertal FHnegative children.
Ključne besede: sex differences, prepubertal children, total cholesterol, low-density lipoprotein cholesterol, familial hypercholesterolemia
Objavljeno v DiRROS: 17.11.2025; Ogledov: 122; Prenosov: 58
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7. Enhanced oral glucose tolerance test for early detection of insulin resistance and metabolic complications in children with obesityUrh Grošelj, Jan Kafol, Jaka Šikonja, Matej Mlinarič, Robert Šket, Žiga Iztok Remec, Jernej Kovač, Ana Drole Torkar, Jasna Šuput, Barbka Repič-Lampret, Tadej Battelino, Primož Kotnik, 2025, izvirni znanstveni članek Povzetek: Background and aims: Early detection of insulin resistance (IR) and obesity-related complications is crucial for preventing type 2 diabetes. This study aimed to identify dynamic metabolic biomarkers for more precise early detection of IR and metabolic abnormalities. Methods: This cross-sectional cohort study evaluated IR and metabolic biomarkers in 403 children with obesity (median age 13.18 years, 51.3 % female, 98.5 % with obesity) using an enhanced oral glucose tolerance test (eOGTT). IR was assessed via four indices, with the Matsuda Insulin Sensitivity Index (ISI-M) used as the primary measure. Participants were stratified into quartiles based on ISI-M. Results: Participants with the highest IR (Q1) were older (p = 0.002), had a higher body mass index, were in a more advanced pubertal stage (p < 0.001), and had significantly elevated glucose and insulin levels (p < 0.001 for both) compared to the most insulin sensitive (Q4), with significant differences observed across all quartiles (p < 0.050 for all). Insulin at 120 min demonstrated excellent diagnostic accuracy for IR (AUC=0.958). Triglyceride levels in Q1 showed minimal decline during the eOGTT, while greater declines were observed with increasing insulin sensitivity (p = 0.002 across quartiles), suggesting that a lack of decline in triglycerides may help identify IR. High-sensitivity C-reactive protein levels increased with IR (p = 0.024). Baseline beta-hydroxybutyrate levels were highest in the Q4 and showed the greatest absolute decrease during the eOGTT, compared to Q1 (p < 0.001 for both). Conclusions: We validated established IR markers in children with obesity, while demonstrating that eOGTT may offer improved characterization and earlier identification of those at risk for metabolic complications.
Ključne besede: insulin resistance, oral glucose tolerance test, OGTT, metabolic complications, screening, children, adolescents, obesity
Objavljeno v DiRROS: 11.11.2025; Ogledov: 185; Prenosov: 73
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8. Continuous glucose monitoring use and glucose variability in pre-school children with type 1 diabetesKlemen Dovč, Kevin Cargnelutti, Anže Šturm, Julij Šelb, Nataša Bratina, Tadej Battelino, 2018, izvirni znanstveni članek Povzetek: Aims. The objective of this nationwide population-based cohort study was to evaluate the correlation between continuous glucose monitoring (CGM) use and glucose variability in pre-schoolers with type 1 diabetes.
Methods. We analysed data from the Slovenian National Registry. The primary endpoint was the difference in glucose variability between periods, during which participants were using CGM and periods, during which CGM was not used, over 5 years. Results. A total of 40 children <8 years old were followed for an estimated observational period of 116 patient/years. Mean age at CGM initiation was 3.5 (±1.7) years. Both standard deviation of mean glucose [3.6 mmol/L (3.2–3.9) with CGM and 4.3 mmol/L (3.8–4.7) without CGM, p < 0.001] and coefficient of variation [44.0% (40.4–47.0) with CGM and 46.1% (42.3–49.4) without CGM, p = 0.021] were lower during the periods, when CGM was used. Frequent CGM use (>5 days/week) was associated with a 0.4% [4.4 mmol/mol] reduction in glycated haemoglobin level (7.6% compared to 7.2%, p = 0.047). Conclusions. Our results indicate that the use of CGM was associated with reduced glucose variability during a 5 year follow-up period among pre-schoolers with type 1 diabetes.
Ključne besede: continuous glucose monitoring, type 1 diabetes, children, insulin therapy
Objavljeno v DiRROS: 12.11.2020; Ogledov: 2315; Prenosov: 1397
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