Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine最新文献

{"title":"Reassessing Vitamin D Deficiency: Data Driven Indirect Reference Intervals for 25-Hydroxyvitamin D in Pakistan via refineR Algorithm.","authors":"Sibtain Ahmed, Amal Mahmood, Ashishkumar Agravatt, Imran Siddiqui, Aysha Habib Khan","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>To establish population-specific reference intervals (RIs) for serum 25-hydroxyvitamin D [25(OH) D] in the Pakistani population using an indirect big data approach, and to evaluate the prevalence of vitamin D deficiency across age and sex strata.</p><p><strong>Methods: </strong>This retrospective study analyzed serum 25(OH) D levels from 201,625 individuals aged ≥18 years who underwent testing at a tertiary care center over five years. Data were extracted from electronic medical records. Serum 25(OH)D was measured via chemiluminescent immunoassay (DiaSorin Liaison), with internal and external quality controls. The refineR algorithm with modBoxCox transformation was used to derive RIs. Statistical analysis was conducted using R software.</p><p><strong>Results: </strong>The median serum 25(OH)D level was 17.2 ng/mL, with 25.7% of individuals classified as deficient (≤20 ng/mL), and 33% severely deficient (≤12 ng/mL). Vitamin D deficiency was more pronounced in men and younger adults. Reference intervals derived using modBoxCox transformation were 10.3-51.5 ng/mL for females and 6.1-50.6 ng/mL for males. Notably, females demonstrated higher vitamin D levels across all age groups compared to males.</p><p><strong>Conclusion: </strong>This study presents large-scale, data-driven estimated reference intervals for 25(OH)D in Pakistan using an indirect approach. The findings highlight a high burden of vitamin D deficiency, particularly among men and younger adults, and reinforce the need for localized reference values to improve diagnostic accuracy. These insights support the development of targeted screening and supplementation strategies, and the reevaluation of clinical thresholds based on population specific data.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"601-608"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statistical Analysis of the Performance of Open-Access Language Models: A Tool in the Clinical Laboratory.","authors":"Micaela Avellaneda, Pamela De Francesco, Nilda Fink","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Artificial intelligence (AI) has been progressively incorporated into the clinical analysis laboratory, optimizing data management, detection of complex patterns, and image-based diagnostic support. Among emerging tools, Large Language Models (LLMs) represent a significant advance by enabling natural language processing for clinical, analytical, and academic tasks. However, their performance is heterogeneous and depends on model architecture, training, and contextual fine-tuning. Objective: To compare the performance of eight openly accessible large language models (LLMs) applied to the biomedical domain by assessing their output quality and inter-rater consistency.</p><p><strong>Materials and methods: </strong>A cross-sectional comparative study was carried out. Eight LLMs (ChatGPT-4, DeepSeek V3.1, Gemini, Copilot GPT-5, Claude 3.5 Haiku, Perplexity AI, DeepAI, and Poe) were queried using six standardized questions regarding the analytical evolution of blood glucose measurement. Responses were evaluated by two independent automated systems (Text Cortex AI and Grok Code Fast 1) using a Likert scale from 1 to 10 and considering eight criteria of textual and scientific quality. Friedman and Wilcoxon-Holm tests were used for global and pairwise comparisons, and Pearson and Spearman coefficients were calculated to assess inter-rater agreement.</p><p><strong>Results: </strong>Significant differences were identified among models (p < 0.001). The LLMs Gemini, DeepSeek, and ChatGPT-4 obtained the highest scores (medians > 8.5), whereas DeepAI and Poe showed lower performance. Inter-rater correlation based on median scores showed a markedly strong linear association (r = 0.91; p = 0.0019) and a robust ordinal agreement (ρ = 0.83; p = 0.011). The least-squares regression line (E2 = 1.37·E1 - 3.25) indicated a sustained positive relationship between the two systems, with balanced dispersion around the linear model. These findings confirm the stability of the evaluation pattern and support the reproducibility of the method.</p><p><strong>Conclusion: </strong>The LLMs with greater complexity and contextual fine-tuning demonstrated superior accuracy, coherence, and reproducibility; however, it is suggested that LLMs may serve as complementary tools depending on the clinical or research context. Their use in healthcare requires methodological validation and expert oversight to ensure safety and clinical applicability within established ethical and regulatory frameworks.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"632-638"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical Clues in unravelling the Puzzle of Anti- synthetase Syndrome.","authors":"Lekha Priyadharshini Kamarajan, Mala Mahto, Sushil Kumar, Deependra Kumar Rai","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Anti-synthetase syndrome (ASSD or ASyS) is a rare, systemic autoimmune disorder characterized by the presence of anti-aminoacyl transfer RNA synthetase (anti-ARS) antibodies, most commonly anti-Jo-1. It presents with a combination of myositis, interstitial lung disease (ILD), arthritis, Raynaud's phenomenon, mechanic's hands, and constitutional symptoms, often posing significant diagnostic challenges. We report the case of a 49-year-old male carpenter who presented with persistent cough, progressive dyspnoea, proximal muscle weakness, and joint pain. High-resolution computed tomography (HRCT) of the chest revealed interstitial lung disease with bilateral basal end-inspiratory crepitations noted on physical examination. Serological testing demonstrated anti-Jo-1 antibody positivity, confirming the diagnosis of anti-synthetase syndrome. The patient was initiated on glucocorticoids, hydroxychloroquine, and steroid-sparing immunosuppressive therapy, resulting in symptomatic and functional improvement. This case underscores the importance of early recognition of anti-synthetase syndrome, particularly in patients presenting with unexplained ILD and musculoskeletal symptoms. Delayed diagnosis is often attributed to limited clinical awareness and the restricted availability of routine testing for anti-ARS antibodies, particularly anti-Jo-1, which significantly affects patient outcomes. ILD is a predominant and serious manifestation of ASyS and remains a strong predictor of disease-related morbidity and mortality. Anti-synthetase syndrome should be considered in patients with interstitial lung disease, muscle weakness, and inflammatory arthritis, especially when anti-Jo-1 antibodies are detected. Early diagnosis and immunosuppressive therapy are critical to improving prognosis and preserving lung function.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"747-752"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Robust Point of Care Testing Program in Newfoundland and Labrador Using Lean Method of Rapid Process Improvement Workshop (RPIW).","authors":"Vinita Thakur, Olatunji Anthony Akerele","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The implementation of a provincial Point-of-Care Testing (POCT) program across Newfoundland and Labrador (NL), Canada, is designed to standardize verification processes and ensure consistent analytical performance of POCT analysers across diverse healthcare settings. The program is developed using a \"Test and Treat\" model to support both remote rural communities and urban populations. Many provincial locations operate as standalone POCT sites hence vendors are required to provide site-specific support services. Selection of analytically robust and cost-effective POCT devices is prioritized to support sustainability and quality patient care. Extensive project planning include Lean Six Sigma methodologies, including Rapid Process Improvement Workshop (RPIW), to standardize workflows and improve operational efficiency. Carefully selected Six Sigma team members participate in collaborative brainstorming sessions to develop streamlined verification and installation strategies across 23 provincial POCT sites. Each analyzer is assigned a Provincial Equipment Unit Identification Number (PEUIN) to enhance traceability and inventory management. Primary verification is conducted centrally at St. Clare's Mercy Hospital, St. John's, while secondary verification is completed at individual installation sites to ensure site-specific performance validation. Harmonized installation of identical analysers support a standardized and quality-driven approach to provincial POCT expansion. Structured utilization management processes are not yet fully established within NL Health Services. Development of utilization monitoring tools to evaluate financial implications and cost-effectiveness is ongoing. Quality improvement initiatives are continuously monitored using key performance indicators. Additionally, the implementation of the EPIC hospital information system in April 2026 provides opportunities for further standardization and integration of POCT processes across the province.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"727-742"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Effects of BMI Adjustment on Ferritin Levels in Anemic Patients.","authors":"Dhivya Baskaran, Jagadish Ramasamy","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of obesity and anaemia is consistently increasing in India. Obesity is a chronic inflammatory state and is associated with dysregulation of iron homeostasis. Ferritin, a marker for cellular iron stores, is also an acute phase reactant that remains elevated during inflammation. Previous studies have used inflammation-adjusted serum ferritin to address this. This current study aims to calculate body mass index (BMI)-adjusted ferritin using a regression correction and evaluate its effects across gender and BMI category in anemic patients.</p><p><strong>Methods: </strong>De-identified data were retrieved from hospital records and laboratory information systems. BMI-adjusted ferritin was estimated using a regression correction formula: ln(adjusted ferritin) = ln(unadjusted ferritin) - β(BMI - median BMI).</p><p><strong>Results: </strong>A total of 458 subjects were included, of whom 62% were female and 95% were anemic. Adjusted ferritin levels were slightly lower than unadjusted levels in the normal BMI group (59.8 vs 60) and in males (102.3 vs 113.75). In contrast, adjusted ferritin levels were marginally higher in the overweight/obese group (29.9 vs 28.9) and in females (22.7 vs 22.1). The percentage change in ferritin following adjustment ranged from -0.33 to 10.07.</p><p><strong>Conclusion: </strong>BMI-based regression correction had differential effects across BMI categories and gender. The adjustment substantially attenuated higher ferritin levels in normal BMI and males. In contrast, a minimal increase was observed in overweight/obese individuals and in females with lower baseline ferritin levels. Notably, the magnitude of these percentage change in ferritin is small relative to the reported within-person biological variation (BV) of ferritin, suggesting limited clinical impact.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"651-658"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unexplained Hypercobalaminemia: A Rare Diagnostic Pitfall.","authors":"Anil K Chokkalla, Kafi B Thomas, Arun Rathinam","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Persistently elevated serum vitamin B12 may suggest underlying pathology once analytical interferences are excluded. Here, we report a case of 56-year-old female with high vitamin B12 levels incidentally noted by primary care provider. Repeat testing with different assay method over time demonstrated consistently high values, prompting further evaluation. Hematology-oncology provider initiates malignancy workup due to well-documented association between neoplastic process and elevated vitamin B12 levels. Concurrently, clinical laboratory was contacted to rule out potential assay interference related to macro-vitamin B12 complexes. A polyethylene glycol precipitation study demonstrated markedly low vitamin B12 recovery, supporting the presence of a macro-vitamin B12 complex as the cause of spurious elevation. This case report highlights the importance of excluding macro-vitamin B12 interference prior to initiating extensive malignancy workup and the lack of evidence-based guidelines for the laboratory assessment of macro-complexes.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"767-770"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis and Correlation of Serum 25-Hydroxyvitamin D3 Levels with Glycemia and Cardiometabolic Risk Factors: A Tertiary Care Hospital-Based Study.","authors":"Amit D Sonagra, Deepak N Parchwani, Anita Motiani, Sagar J Dholariya, Ragini Singh, Krupal J Joshi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Role of Vitamin D is not limited to skeletal health but it acts as a potential modulator of metabolic homeostasis. Studies have shown its influence on insulin secretion and cardiometabolic risk factors. This study was conducted to evaluate correlation of serum 25-hydroxy vitamin D3 (25OH VitD3) levels with glycemic status and lipid profile parameters in a tertiary care hospital setting.</p><p><strong>Methods: </strong>A cross-sectional observational study was conducted taking 173 adults (>18 years) attending outpatient department of a tertiary care hospital between April and December 2025. Participants were categorized based on HbA1c levels according to American Diabetes Association criteria into non-diabetic, pre-diabetic, and diabetic. 25OH VitD3, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were estimated from fasting serum sample. Statistical analyses were performed and statistical significance was set at p<0.05.</p><p><strong>Results: </strong>Vitamin D deficiency and insufficiency were observed in more than 65% of participants (mean 25OH VitD3: 27.8±16.16 ng/mL). Patients with diabetes mellitus showed significantly higher TG, VLDL, TG/HDL and TC/HDL ratios and lower HDL levels (p<0.05). 25OH VitD3 showed a weak statistically significant negative correlation with HbA1c (ρ = -0.186, p=0.014) but no significant correlation with lipid parameters. Regression models revealed moderate explanatory power (R²: 23.9-28.4%), with classical metabolic markers contributing more than vitamin D.</p><p><strong>Conclusion: </strong>A high prevalence of vitamin D deficiency was detected. Vitamin D demonstrated a weak correlation with glycemia and no correlation with lipid parameters. Vitamin D may function as a metabolic modulator rather than a primary determinant of dysglycemia and dyslipidemia.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"639-650"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Sweat Conductivity Testing and Referral Patterns for Cystic Fibrosis: A 10-Year Retrospective Single-Center Study in Albania.","authors":"Hamide Shllaku-Sefa, Teuta Dedej-Kurti, Ndok Marku","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Cystic fibrosis (CF) is an autosomal recessive disorder. Sweat testing is a cornerstone of CF diagnosis and remains essential in settings where nationwide screening and registries are limited.</p><p><strong>Materials and methods: </strong>We performed a retrospective single-center analysis of all patients referred for sweat testing in our laboratory between May 2015 and May 2025 (n=567). Sweat induction and collection were performed using the Macroduct® system, and analysis was conducted via the Sweat-Chek™ Analyzer (Model 3120, ELITechGroup). Statistical analysis was performed using Jamovi software (version 2.3.28).</p><p><strong>Results: </strong>The cohort included 302 males (53%) and 265 females (47%), with a mean age of 36.3 ±49.2 months (Median: 14; IQR: 4-48). The primary indications for referral were respiratory manifestations (57%), followed by gastrointestinal symptoms (14.1%), failure to thrive (6.2%), and others (4.2%). Asymptomatic individuals with no symptoms recorded at referral (18.2%). Diagnostic outcomes revealed that 83.4% of participants had normal results, 11.3% were positive, and 3% were borderline. A \"quantity not sufficient\" (QNS) rate of 2.3% was observed.</p><p><strong>Conclusions: </strong>In this single-center referral cohort, most sweat test results were normal, with an overall positive rate of 11.3% and low QNS rates that are benchmark favorably against published quality targets. Clear referral pathways and strengthened early-life evaluation (including expansion of screening access) may support earlier diagnosis and reduce disease burden.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"592-600"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Hemolysis on UCH-L1 Quantification in Serum and Plasma.","authors":"Paula García Martín, Silvia Álvarez Rodríguez, Covadonga Solar Macarro, Rafael Venta Obaya, Eduardo Martínez-Morillo","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a neuron-enriched deubiquitinase widely used for the evaluation of mild traumatic brain injury (TBI). Although minimal hemolysis-related interference has been reported for the Abbott TBI assay, routine laboratory observations indicate that hemolysis may substantially influence UCH-L1 measurements. This study aimed to evaluate the effect of hemolysis on UCH-L1 concentrations in plasma and serum samples and its potential clinical implications.</p><p><strong>Methods: </strong>Hemolysis interference was evaluated in accordance with CLSI C56-A and EP07 guidelines using pooled plasma samples and paired individual patient samples. Controlled hemolysis was induced by adding graded amounts of erythrocyte hemolysate to non-hemolyzed samples. UCH-L1 concentrations were measured using the Abbott Alinity i system. In addition, a retrospective analysis of routine TBI biomarker requests was conducted to estimate the potential rate of hemolysis-induced false-positive results.</p><p><strong>Results: </strong>In pooled plasma, UCH-L1 increased linearly (R² = 0.992) with the hemolysis index (HI), with a 10% analytical bias observed at HI values of 100 or lower. Erythrocyte-derived samples showed UCH-L1-related signals more than 20-fold higher than plasma. In individual patient samples, hemolysis induced a dose-dependent but highly variable positive bias. Retrospective analysis suggested that hemolysis could result in false-positive UCH-L1 results in up to 21.5% of TBI-negative patients with concentrations near the clinical cut-off.</p><p><strong>Conclusions: </strong>Hemolysis induces a clinically relevant positive bias in UCH-L1 measurements, even at moderate HI levels. These findings underscore the importance of strict preanalytical control and cautious interpretation of UCH-L1 results obtained from hemolyzed samples.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"667-676"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infantile Osteopetrosis with a CLCN7 Variant: An Educational Case Highlighting Integrated Diagnosis and Variant Interpretation.","authors":"Shree A V Meena, Ranjith Kumar Manokaran, Dhaarani Jayaraman, Jai Prakash Srinivasan, Elayaraja Sivaprakasam","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Infantile osteopetrosis is a rare inherited disorder caused by defective osteoclast-mediated bone resorption, resulting in increased bone density and marrow failure. The CLCN7 gene encodes a chloride channel essential for osteoclast acidification.</p><p><strong>Case presentation: </strong>A 4-month-old male presented with failure to thrive, pallor, hepatosplenomegaly, and recurrent infections. Examination revealed frontal bossing and hypotonia. Laboratory evaluation showed anemia and persistent hypocalcemia (6.8 mg/dL; reference 8.5-10.5 mg/dL). Skeletal survey demonstrated diffuse osteosclerosis with a characteristic \"bone-within-bone\" appearance. Differential diagnoses, including storage disorders and leukemia, were excluded. Clinical exome sequencing identified a homozygous CLCN7 missense variant, c.613G>A (p.Gly205Arg), classified as a variant of uncertain significance (VUS) based on ACMG/AMP criteria (PM2, PP3).</p><p><strong>Conclusion: </strong>Diagnosis in this case was primarily clinico-radiological, with genetic findings providing supportive evidence. This report presents an educational case emphasizing the importance of integrated clinical, radiological, and laboratory evaluation, and highlights the challenges in interpreting variants of uncertain significance in clinical practice.</p>","PeriodicalId":37192,"journal":{"name":"Electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine","volume":"37 4","pages":"753-758"},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}