OBJECTIVES:Anti-Müllerian hormone (AMH) is a dimeric glycoprotein essential for male sex differentiation during embryogenesis and a widely used biomarker of testicular function in adult men. This study aimed to determine within-subject (CVI) and between-subject (CVG) biological variation data for serum AMH in healthy adult men. METHODS:Between November 2024 and March 2025, this Turkey-based study enrolled 20 healthy adult male volunteers selected using predefined inclusion and exclusion criteria. Blood samples were collected over four consecutive weeks, resulting in four specimens per participant. The serum AMH concentration was analyzed on a Roche Cobas e601 analyzer. Statistical analyses included outlier detection; assessment of data distribution, steady-state conditions, and homogeneity; analysis of variance with a 95% confidence interval (CI); estimation of analytical performance specifications (APSs); and calculation of the individuality index (II) and reference change value (RCV). RESULTS:CVI was 3.5% (95% CI: 2.93-4.3), while CVG was 34.72% (95% CI: 26.38-50.75) in this study. The II value was 0.1, and the asymmetrical RCV was +9% for increases and - 8.2% for decreases. Desirable APSs were imprecision <1.75%, bias <8.72%, and total allowable error < 11.61%. CONCLUSIONS:The low CVI for AMH in men indicates stringent homeostatic regulation. The low II signifies high individuality, suggesting that RCV utilization is more appropriate than population-based reference intervals for clinical monitoring. To the best of our knowledge, this is the first comprehensive study reporting biological variation data for AMH in men.

The melanoma pathophysiology is considerably complex. Wnt signaling via the β-catenin/transcription factor 7-like 2 (TCF4)/Lymphoid enhancer-binding factor 1 (LEF1) complex, the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-2 (TRP-2), tyrosinase (Tyr) and cyclin-dependent kinase 2 (Cdk2) are reported to activate the transcriptional gene expression associated with pigmentation and the differentiation and proliferation of melanocytes and malignant melanoma cells. Cinobufagin is a leading active ingredient in Traditional Chinese Medicine, and has been approved in China as a chemotherapeutic agent for the treatment of liver and prostate cancer. The primary aim of the present study is to evaluate the effects of cinobufagin and paclitaxel on melanoma cells, both individually and in combination, in the G361 melanoma cell line. Within the scope of the study, IC50 doses were determined based on an MTT analysis, Caspase-3 measurements were analyzed using the ELISA method and mRNA expression levels were analyzed using the RT PCR method. Cinobufagin used in combination with paclitaxel was found to increase Caspase-3 levels more than when cinobufagin was used alone, and it was further determined that cinobufagin treatment decreased the expression levels of the β-catenin, C-myc and Cyclin D1 genes, while paclitaxel and cinobufagin used in combination were found to increase all mRNA expression levels (Bax, Caspase-3, Bcl2, β-catenin, C-myc, Wnt and Cyclin D1). Cinobufagin can be considered a promising natural pharmaceutical agent for the targeted treatment of cancers with high levels of LEF1.

Introduction:Free amino acid (FAA) analysis plays a crucial role in diagnosing and monitoring inborn errors of metabolism, assessing nutritional status, and identifying metabolic imbalances associated with various diseases. This study aimed to provide updated biological variation (BV) data to support the reliable clinical application of FAA concentrations in plasma samples, utilizing LC-MS/MS. Materials and methods:Venous blood was collected from 22 healthy Turkish adults (9 men and 13 women) over approximately nine weeks. Plasma FAAs were measured in duplicate. BV estimates with 95 % confidence intervals were determined using nested ANOVA for the entire study group and sex-stratified subgroups, following analysis of outliers, normality, steady-state conditions, and variance homogeneity. Results:Within-subject variation (CVI) and between-subject variation (CVG) estimates ranged from 9.5 % to 32.5 % and 8.6 % to 50.0 %, respectively. The estimated CVI values for essential amino acids were significantly lower than those for non-essential amino acids (P = 0.03). For most plasma FAAs, no significant differences in CVI (except for alanine, arginine, glutamic acid, and threonine) or CVG were observed between sexes. However, differences in the indices of individuality were noted between men and women for some plasma FAAs. Conclusions:This Biological Variation Data Critical Appraisal Checklist-compliant study provides the first updated BV data for plasma FAAs. The significant variation observed in CVI estimates is hypothesized to result from differences in the metabolic regulation of essential versus non-essential amino acids. The sex-stratified indices obtained in this study will aid in the appropriate application of population-based reference intervals for plasma FAA assessment.

Understanding biological variation (BV) is crucial for accurate clinical decision-making and for establishing analytical quality standards. This study established the BV of low-density lipoprotein cholesterol (LDL-C), assessed using both direct measurement and calculated values obtained from the Friedewald and Martin-Hopkins formulas in healthy individuals. A total of twenty-six healthy Turkish subjects (15 females and 11 males) underwent fasting LDL-C measurement, along with calculated LDL-C derived from serum cholesterol, triglycerides, and high-density lipoprotein cholesterol, using samples collected concurrently on 10 weekly occasions. All measurements were conducted in duplicate by the enzymatic colorimetric method. Within-subject (CVI) and between-subject (CVG) BV estimates, with 95% confidence intervals (CI), were determined by CV-ANOVA following evaluation of trends, homogeneity of variance, and outlier removal. No significant gender-related differences were observed in the BV components for either direct or calculated LDL-C. According to direct LDL-C, Friedewald LDL-C, and Martin Hopkins LDL-C, CVI values were 8.7%, 9.3% and 9.0%, and the CVG values were 14.7% for direct LDL-C, 18.5% for Friedewald LDL-C, 18.6% for Martin Hopkins LDL-C. These values supported the use of updated analytical performance specifications and reference change values (RCV). All LDL-C exhibited marked individuality (II < 0.6). By applying a rigorously standardized experimental protocol, the inter-individual variability observed supports the preferred use of RCVs over conventional population-based reference intervals for serial monitoring. These results have important implications for enhancing the clinical utility of LDL-C measurements, regarding cardiovascular risk assessment and individualized therapeutic decision-making.

OBJECTIVES:Serum cholinesterase (ChE) 3.1.1.8 is measured to assess exposure to organophosphorus pesticides and determine deficiency related to prolonged apnea after the induction of anesthesia with certain drugs and less often as an indicator of liver function. Biological variation (BV) is an accepted endogenous source that contributes to the total variation in laboratory medicine. No data on the BV of serum ChE have been found in the European Federation of Clinical Chemistry and Laboratory Medicine BV database. Thus, this study aimed to contribute to the data on BV of serum ChE activity. METHODS:Detailed inclusion and exclusion criteria were used for the enrollment of 20 (10 women and 10 men, 8-10 weeks) ostensibly healthy volunteers from Turkey. The serum ChE activity was measured on Roche Cobas c501. Statistical analyses included the detection of outliers, control for the normality of distribution, checking steady-state condition, assessment for homogeneity, subgroup analysis, analysis of variance with 95 % confidence intervals, and estimation of analytical performance specifications (APS). RESULTS:After exclusion, 332 results were included in the study. The within-subject BV of men (3.5 % [2.9-4.2 %]) was lower than that of women (4.8 % [4.1-5.8 %]). Between-subject BV of men and women were 15.9 % [10.5-32.4 %] and 12.3 % [8.4-22.6 %], respectively. The index of individuality was 0.18 and reference change value (RCV) was +9.1 %/-8.3 %. The calculated desirable APS for imprecision and bias were 1.7 and 3.2 %, respectively. CONCLUSIONS:We believe that this study will contribute to the BV data on serum ChE activity. The prominent individuality of serum ChE activity favors the use of RCV instead of population-based reference intervals for more reliable follow-up.

AMAÇ: Kalite göstergeleri (KG), hata oranlarını azaltarak ve hasta güvenliğini koruyarak laboratuvar hizmetlerinin kalitesini iyileştirmek için kullanılan temel araçlardır. Çalışmamızda, acil servisten gelen ve reddedilen kan numunelerinin sayı ve oranları incelenerek IFCC’ nin (Uluslararası Klinik Kimya ve Laboratuvar Tıbbı Federasyonu) “Laboratuvar Hataları ve Hasta Güvenliği” Çalışma Grubu’nun (WG-LEPS) rapor ettiği kalite indekslerine göre karşılaştırılması amaçlandı. GEREÇ VE YÖNTEM: Acil servisten Klinik Biyokimya Laboratuvarı'na gelen kan numunelerinin sayılarını değerlendirmek için, 2022 yılına ait veriler Laboratuvar Bilgi Sistemi’nden (LBS) geriye dönük olarak alındı. Analiz öncesi aşamada, laboratuvara gelen kan örneklerinin sayıları, reddedilme nedenlerine göre gruplandırılarak aylık ve yıllık yüzdeleri hesaplandı. IFCC WG-LEPS’nin üç hedef kriterlerini içeren ölçütler (%25’lik yüksek performans, %50’lik orta dereceli performans ve %75’lik düşük performans) kapsamında değerlendirildi. BULGULAR: Toplam numune ret oranı % 2,3 olarak hesaplanmıştır. Reddedilme nedenlerine göre “hemolizli numune”, “uygun olmayan numune kabı”, “uygun olmayan numune miktarı” ve “pıhtılı numune”’ lerin % KG değerleri sırasıyla 0,72, 0,03, 0,77 ve 0,80 olarak belirlendi. SONUÇ: Laboratuvarımızın “hemolizli numune” ve “uygun olmayan numune kabı’’ için % KG’sinin düşük performansa sahip olduğu gösterildi. “Pıhtılı numune” ve “uygun olmayan numune miktarı” için % KG’lerinin kabul edilemez aralıkta olduğu tespit edildi. Sonuç olarak, numune alımı ve transferi konularındaki eğitimlerin sıklığı artırılarak, sürecin kalitesinin artırılacağı düşüncesindeyiz.

Serum light immunoglobulin chains (LCs) are critical biomarkers for the diagnosis, prognosis, and treatment response monitoring in monoclonal plasma cell dyscrasias. Robust performance standards based on biological variation (BV) data are essential for optimizing patient care. This study aimed to provide updated BV estimates for serum free LCs (κ and λ) as well as their κ/λ LC ratio. Serum samples from 25 healthy volunteers (10 men, 15 women) were collected weekly over approximately 9 weeks. Serum free LCs were measured in duplicate using the Roche Cobas c501 analyzer. BV estimates with 95 % confidence intervals were calculated using coefficient of variation (CV) in ANOVA for the entire group and by sex, following assessments for outliers, normality, steady-state conditions, and variance homogeneity. The within-subject BV (CVI) estimates were 9.2 %, 8.6 %, 6.6 % for free κ, free λ, free κ/λ ratio, respectively. The between-subject BV (CVG) estimates were 24.6 %, 26.6 %, and 17.5 %for free κ, free λ and free κ/λ ratio, respectively. No significant sex differences were observed for CVI with the exception of free κ and free κ/λ ratio or CVG in serum free LCs and their ratio. Free LCs and their κ/λ ratio exhibited marked individuality. Analytical performance specifications (APSs) for desirable imprecision and bias ranged 3.9 %-5.4 %, 4.3 %-5.8 % and 2.9 %-4.6 % for free κ, free λ and free κ/ λ ratio, respectively. This study provides updated, well-characterized BV estimates for serum free (κ and λ) and free κ/λ ratio, providing essential data to define APSs. The individuality of κ and λ underscores the importance of prioritizing reference change values over traditional reference intervals for improved diagnosis and monitoring in clinical practice.

Objectives The aims of this study were to determine the biological variation (BV), reference change value (RCV), index of individuality (II), and quality specifications for serum neopterin concentrations; a measurand provided by clinical laboratories as an indicator of cellular immunity.Methods The study delivered serum samples collected for 10 consecutive weeks from 12 apparently healthy individuals (3 male, 9 female). Serum neopterin concentrations were measured using high-performance liquid chromatography with fluorometric detection. The data analysis was performed using an online statistical tool and addressed published criteria for estimation of biological variation.Results The mean neopterin concentration was 5.26 nmol/L. The within-subject biological variation (CVI) with 95 % confidence interval (CI) of neopterin serum concentrations was 11.54 % (9.98-13.59), and the between-subject biological variation (CVG) with 95 % CI was 43.27 % (30.52-73.67). The neopterin asymmetrical RCV was -24.9 %/+33.1 %, and the II was 0.27. The desirable quality specifications for neopterin were <5.77 % for precision, <11.20 % for bias, and <20.72 % for total allowable error (TEa). When analytical variation was used instead of CVI to calculate TEa, the desirable TEa was <18.39.Conclusions This study determined BV data for neopterin, an indicator of cell-mediated immune response. Asymmetric RCV values, of 24.9 % decrease or a 33.1 % increase between consecutive measurements indicate significant change. The II of 0.27 indicates a high degree of individuality, therefore that it is appropriate to consider the use of personal reference data and significance of change rather than the reference interval as points of reference for the evaluation of neopterin serum concentrations.

Purpose: Biotinidase deficiency (BD) is a rare autosomal recessive metabolic disorder that impairs the body's ability to recycle biotin, a crucial coenzyme for carboxylase enzymes involved in various metabolic processes. This study aims to evaluate the effects of biotinidase deficiency on cholinesterase activity in plasma, hypothesizing that the metabolic disruptions caused by inadequate biotin recycling may lead to alterations in cholinesterase function. Materials and methods: Plasma samples were collected from 73 individuals categorized into four genetic groups: wild type (n = 12), heterozygous (n = 30), homozygous (n = 19), and compound heterozygous (n = 12). Cholinesterase activity was measured using a colorimetric method. Results: The study discovered that the cholinesterase activity of the Heterozygous group was higher than the homozygous group (p = 0.0356). Additionally, cholinesterase activity was significantly lower in homozygous and compound heterozygous people than in wild and heterozygous groups (p = 0.0272). The statistically significant changes suggested a relationship between biotinidase deficiency and altered cholinergic activity. Conclusion: The findings indicate that biotinidase deficiency, particularly in its severe variants, may cause considerable reductions in cholinesterase activity, contributing to the neurological symptoms found in affected patients. More studies are needed to investigate the processes behind this association and develop strategies for reducing the effects of BD on cholinesterase activity and neurological health.

Aim: Obesity is a condition that occurs as a result of excessive weight gain. Obesity is related with the high risk of several diseases like cardiovascular diseases and diabetes mellitus. Elabela is a peptide that has emerged recently and is known to affect food intake by binding to apelinergic receptors. This study aimed to investigate the serum levels of Elabela in obese and non-obese individuals. Material and methods: This study involved 24 people with obesity and 25 healthy adult people as control group. Height, weight, gender, age, waist-hip circumference, blood pressure of participants were recorded and routine blood tests were measured. Serum concentrations of Elabela were determined using enzyme-linked immunosorbent assay. Results: When comparing the obese group to the controls, no statistically significant differences were observed between the two groups in terms of diastolic blood pressure, blood urea nitrogen, creatinine, total cholesterol, low density lipoprotein cholesterol and C-reactive protein. Similarly, both groups did not differ statistically regarding Elabela levels. The obese group exhibited significantly elevated levels of body mass index, waist/hip ratio, systolic blood pressure values, glucose, aspartate aminotransferase, alanine aminotransferase, triglyceride, insulin, homeostatic model assessment for insulin resistance (HOMA-IR) compared to the control group. The obese group demonstrated a significantly lower level of high-density lipoprotein cholesterol in comparison to the control group. Conclusions: In this study, it was found that there was no relationship between Elabela levels and obesity. However, this issue needs to be supported by further studies to clarify.

Objectives: We aimed to investigate the usability of pleural pyruvate kinase (PK), total antioxidant status (TAS), and total oxidant status (TOS) as an alternative to Light's criteria in exudate-transudate differentiation. Methods: This prospective study was conducted among 84 patients (42 transudates and 42 exudates) with pleural effusion. The levels of PK, TAS, and TOS were measured by using ELISA kits, and the ROC analysis was used to evaluate the diagnostic efficiency. Results: PK (p=0.001), TAS (p=0.027), and TOS (p=0.002) levels in pleural fluids were found to be significantly higher in the exudate group. The cut-off values for PK, TAS, and TOS were 10.64 U/L, 13.54 mmol trolox equivalent/L, and 13.88 mu mol H2O2 equivalent/L, respectively. While the sensitivity values were 97.62 % for PK, 66.67 % for TAS, and 64.29 % for TOS, the specificity values were 80.95 % for PK, 52.38 % for TAS, and 57.14 % for TOS. Conclusions: PK levels in pleural effusion can be useful in suspected cases to differentiate between exudate and transudate in addition to Light's criteria. However, pleural TOS and TAS parameters could not be as sensitive and specific as Light's criteria.

Obtaining suitable results unaffected by preanalytical factors is crucial for laboratory test results. Measurement of parathyroid hormone (PTH) is essential in the evaluation and management of calcium metabolism disorders. The aim of the present study is to evaluate the effects of preanalytical factors such as sample type, storage time and temperature on PTH measurement in the same protocol. Blood samples were collected from 30 healthy volunteers into Serum Separator Tubes (SST), Barricor plasma tubes and EDTA aprotinine tubes. Serum and plasma were analysed immediately after collection simultaneously in the same batch and stored at room temperature RT (250C) and at (40C) for 24 and 48 hours until reanalysis for PTH on DXI800 autoanalyser (Beckman Coulter, USA). Changes in different tubes under different storage conditions were recorded and compared to each other. Clinical decision levels were estimated using analytical desirable bias and reference change value(RCV). No difference was found between tubes in terms of intact PTH levels. From a statistical standpoint, intact PTH level was no longer stable after storage for 24, and 48, hours at 4 C° and 25 C° in both serum tubes and barricor tubes. However, the variations especially in barricor tubes were under analytical desirable bias limits at 4 C0 for 24 hours (-10.48%), and 48 hours (-15.42%) hours and the changes were also not clinically significant. Our results have shown that Barricor tubes are stable at 4 C° up to 48 hours.The stability of the measurements were both analytically and clinically acceptable.

In this study, ballistic performance of adhesively-bonded Single Lap Joints is investigated experimentally and numerically. Using a specially-designed experimental set-up, a projectile with mass of 1.25 gr and density of 11.3 gr/cm3 was fired to the joints at a velocity of 288 m/s. The joints with a thickness of 4 mm and two different overlap lengths, 15 mm and 25 mm, were first subjected to the ballistic and then to the quasi-static tensile tests. When the impacted joints were compared to the non-impacted ones, it was found that while the joints with the 15 mm overlap length mechanically deteriorated, those with the 25 mm length were not affected. These results were validated numerically via the ABAQUS package program. Johnson Cook behaviors of the materials were used as input data in the analysis.

Abstract Objectives Calculation of biological variation (BV) components is very important in evaluating whether a test result is clinically significant. The aim of this study is to analyze BV components for copper, zinc and selenium in a cohort of healthy Turkish participants. Methods A total of 10 serum samples were collected from each of the 15 healthy individuals (nine female, six male), once a week, during 10 weeks. Copper, zinc and selenium levels were analyzed by atomic absorption spectrometer. BV parameters were calculated with the approach suggested by Fraser. Results Analytical variation (CVA), within-subject BV (CVI), between-subject BV (CVG) values were 8.4, 7.1 and 4.3 for copper; 4.2, 9.1 and 13.7 for zinc; 7.6, 2.5 and 6.9 for selenium, respectively. Reference change values (RCV) were 30.46, 27.56 and 22.16% for copper, zinc and selenium, respectively. The index of individuality (II) values were 1.65, 0.66 and 0.36 for copper, zinc and selenium, respectively. Conclusions According to the results of this study, traditional reference intervals can be used for copper but we do not recommend using it for zinc and selenium. We think that it would be more accurate to use RCV value for zinc and selenium in terms of following significant changes in recurrent results of a patient.

Purpose: Preeclampsia (PE) is a pregnancy-specific syndrome characterized by placentation disorder that increases maternal and fetal morbidity and mortality. Overproduction of anti-angiogenic factors such as soluble fms-like tyrosine kinase receptor 1 (sFlt-1) and soluble endoglin (sEng) and low production of placental growth factor (Pgf) from angiogenic factors contribute to preeclampsia pathogenesis. In this study, factors involved in angiogenesis including sEng, Pgf and sFlt1 were investigated for pre-recognition of preeclampsia. Methods: A total of 54 pregnant women were included in the study and the patients were divided into normotensive (n = 25) and preeclampsia groups (n = 29). Both groups demographic characteristics, laboratory parameters, sEng, sFlt1 and placental growth factor levels were compared. Results: While AST, uric acid, LDH mean values were significantly higher in the study group compared to the control group (p<0.05), there was no significant difference between the groups in terms of ALT, creatinin, hemoglobin, leucocyte, and platelet values. sEng, sFlt1 values were significantly lover in the preeclampsia group compared to the control group (p<0.05). Conclusion: it is thought that Pgf may have a place in the prediction of preeclampsia in advanced pregnancy weeks, but sFlt-1 and sEng are weak in predicting preeclampsia in advanced pregnancy weeks as well.

D-dimer is considered to be a reliable marker of both coagulation activation and fibrinolysis. However, data on biological variation (BV) of D-dimer is still limited, causing the use of empiric analytical performance specifications and lack of other implications related to BV. This study aimed to estimate the BV of plasma D-dimer employing a study design compliant with The Biological Variation Data Critical Appraisal Checklist. Blood samples were collected from a cohort of 25 healthy subjects (16 females, 9 males; age range, 19-61 years) from Turkey once weekly for 3 consecutive weeks. All plasma samples were analyzed in duplicate within a single run on Roche Cobas c501. The results were assessed for outliers, variance homogeneity, normal distribution, and trend, followed by nested ANOVA to determine BV and analytical variation estimates with confidence intervals (CIs). Gender stratified BV estimates were also calculated. Within-subject (CVI) and between-subject (CVG) BV estimates with 95% CIs were for D-dimer 21.2% (17.8-25.9) and 30.9% (21.3-46.2), respectively. No significant BV differences were observed between females and males. The index of individuality (II) and the reference change value (RCV) were calculated as 0.71 and 60.4%, respectively. Analytical performance specifications for desirable imprecision, bias, and total error were 10.6, 9.4, and 26.8%, respectively. This study provides well-characterized BV estimates for D-dimer, which may be helpful for setting objectively analytical performance specifications. Moreover, RCV should be preferred to decide whether a significant difference is present between serial D-dimer measurements from an individual.

PURPOSE:The telomere length is shown to act as a biomarker, especially for biological aging and cardiovascular diseases, and it is also suggested that with this correlation, increased exposure to the oxidative stress accelerates the vascular aging process. Therefore, this study aims to understand the correlation between the plasma oxidative stress index (OSI) status and leukocyte telomere length (LTL) and cardiologic parameters between the ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) groups. METHOD:One hundred one newly diagnosed patients with STEMI (n = 55) and NSTEMI (n = 46) were included in the study, along with 100 healthy controls who matched the patients in terms of age and gender. Plasma total antioxidant status (TAS), total oxidant status (TOS), and LTL were measured. RESULTS:When LTL, TAS, TOS, and OSI values were evaluated between the patient and control group, OSI (p = 0.000) and LTL (p = 0.05) values were statistically significant in the patient group compared to the control group. Evaluation was conducted to understand whether there is a difference between the STEMI and NSTEMI groups. The plasma OSI (p = 0.007) and LTL (p = 0.05) were found to be significantly lower in STEMI patients. However, LTL and OSI results were not statistically significant in NSTEMI patients. CONCLUSION:This is the first study evaluating telomere length and oxidative stress in STEMI and NSTEMI patients in Turkey. Our results support the existence of short telomere length in STEMI patients. Future studies on telomere length and oxidative stress will support the importance of our findings.

Aim: Silicosis has long been recognized as an important occupational lung disease that is included in the group of pneumoconiosis. As already well-known silicosis is a progressive pneumoconiosis characterized by fibrosis in the lungs. Also, chronic exposure to silica may cause chronic obstructive pulmonary disease, emphysema, lung cancer, and pulmonary fibrosis. Asymmetric dimethyl arginine (ADMA), symmetric dimethyl arginine (SDMA), and L-NMMA (NG-mono-methylated-L-arginine) are the products of protein arginine methyltransferase (PRMT) enzymes. The aim of this study is to investigate the relationship between silicosis and arginine metabolites in silica exposed and non-exposed workers. Material and Method: 180 male subjects (90 non-exposed workers (age matched-control) and 90 workers diagnosed with silicosis occupational physician based on radiological and clinical findings and exposure history-(silica-exposed) were included in this study. The serum levels arginine, ADMA, SDMA, and L-NMMA were determined using enzyme-linked immunosorbent assay. Results: ADMA, SDMA, L-NMMA values were significantly higher in the silica-exposed group compared to the control group. The positive correlations were observed between methylated arginine parameters such as ADMA and SDMA, ADMA and L-NMMA levels (r=0.43, r=0.60; p

OBJECTIVE:To identify the biotinidase (BTD) gene mutations in patients with biotinidase deficiency in our region; and to determine the phenotype-genotype correlations in the presence of clinical findings.STUDY DESIGN:Descriptive study.PLACE AND DURATION OF STUDY:Department of Medical Genetics and Pediatric Metabolism Outpatient Clinic, Faculty of Medicine, Harran University, between January 2018 and June 2020.METHODOLOGY:Two hundred and nine patients, who were found positive for biotinidase deficiency in heel blood screening, were included. Genomic DNA was isolated from peripheral blood. Next-generation DNA sequencing analysis was performed using primers covering the exon regions of the BTD gene. The results were analysed by the mutation surveyor programme.RESULTS:The most common mutation was c.1330 G>C (p.D444H) and the second most common mutation was c.470 G>A (p.R157H). The majority of the mutations are missense; and they are especially located in the exon 4. The most frequent mutations were found to be D444H and R157H with a rate of 66.66% in symptomatic patients.CONCLUSION:Common mutations in BTD deficiencies were indentified. Associating them with phenotype-genotype data will assist clinicians in better genetic counselling and management in the future by implementing prevention programmes. Key Words: Biotinidase deficiency, BTD gene, Newborn screening, Inherited metabolic disease, Newborn screening programme.