Murat Karaoglan

Background: Growth hormone (GH) stimulation tests have limited diagnostic precision in childhood short stature (SS), and the relationships among endocrine phenotype, GH1 variation, and long-term treatment response remain unclear. We examined the clinical, endocrine, genetic, and five-year growth outcomes of children receiving recombinant GH. Methods: In this retrospective cohort study, 74 children with SS were classified as idiopathic SS (ISS; n = 28) or growth hormone deficiency (GHD; n = 46) using available GH stimulation-test results together with the integrated clinical, auxological, biochemical, radiological, and treatment-eligibility assessments documented in the medical records. Results: Median annual height velocity was 9.0 cm/year, median height gain was 1.80 standard deviation scores (SDS), and median IGF-1 increased from 125.5 to 306 µg/L. GH dose, endocrine parameters, annual height velocity, height gain SDS, and mean post-treatment height and weight gain did not differ significantly between groups. Height and weight increased over follow-up (both p < 0.001), with no significant group or time-by-group interaction. GH1 sequencing predominantly identified common promoter/upstream and intronic polymorphisms; no pathogenic or likely pathogenic variants were detected. Exploratory genetic clustering showed no clinically meaningful association with endocrine phenotype or treatment response. Conclusions: Adjusted models detected no statistically significant between-group differences in height or weight trajectories. This finding does not establish equivalent treatment efficacy.

Background: Leptin integrates metabolic and reproductive signaling later in life; however, whether maternal metabolic cues influence early neonatal hypothalamic–pituitary–gonadal (HPG) axis activity remains unclear. Objective: To evaluate associations between maternal metabolic markers and early neonatal reproductive hormone activity. Methods: Forty healthy term neonates (20 males) were prospectively evaluated. Maternal venous blood samples were collected at delivery, and neonatal blood samples were obtained within the first 24 h after birth. Maternal and neonatal adipokines and reproductive hormones were analyzed using correlation and simplified multivariable regression analyses. False discovery rate (FDR) correction using the Benjamini–Hochberg procedure was applied for multiple testing. Results: Maternal leptin was positively associated with neonatal leptin concentrations ( r = 0.52, p = 0.001; adjusted β = 0.47, p = 0.001), supporting maternal–neonatal metabolic continuity. However, maternal leptin was not significantly associated with neonatal LH concentrations ( β = 0.00009, p = 0.347). Sex remained the strongest independent predictor of neonatal LH levels ( β = 1.21, p = 0.011). Neonatal leptin was positively associated with triceps skinfold thickness ( β = 1503.14, p = 0.034). Most exploratory associations did not remain statistically significant after FDR correction. Conclusions: Maternal metabolic markers were associated with neonatal metabolic parameters but were not strongly associated with early neonatal gonadotropin levels in this cohort. Larger longitudinal studies are required to clarify potential interactions between metabolic and reproductive pathways during later phases of mini‐puberty.

Objective: Type 1 Diabetes Mellitus (T1DM) is an autoimmune condition characterized by progressive pancreatic β-cell destruction, with high familial clustering rates. Siblings of index cases with T1DM represent a critical population for understanding immunogenetic mechanisms, as they share genetic backgrounds while demonstrating variable disease expression. Islet-specific autoantibodies and human leukocyte antigen (HLA) haplotypes are pivotal markers for early risk identification in at-risk siblings. This study aimed to characterize and compare immunological signatures between pediatric index cases with T1DM and their unaffected siblings, with particular emphasis on the utility of combined autoantibody and HLA profiling for predicting disease risk in the sibling population. Methods: A retrospective cross-sectional study was conducted with 230 participants (46 index cases with T1DM and 184 unaffected siblings) recruited from a tertiary pediatric endocrinology clinic. Serum levels of anti-glutamic acid decarboxylase antibodies (anti-GAD), anti-islet cell antibodies (anti-ICA), anti-insulin autoantibodies (anti-IAA), insulin, C-peptide, and glycated hemoglobin (HbA1c) were measured. HLA-DR and -DQ loci were genotyped using high-resolution sequence-based typing. Results: Index cases with T1DM had significantly higher positivity and titers for anti-GAD and anti-ICA (p<0.001), lower C-peptide (0.21 vs. 0.99 ng/mL) and insulin levels (2.87 vs. 4.37 µIU/mL), and elevated HbA1c (11.6% vs. 5.5%) compared to controls. Decision tree analysis identified specific HLA alleles (e.g., DR3-DQ2 and DR4-DQ8) associated with disease status. Conclusion: This study suggests that combined autoantibody profiling and HLA genotyping may be useful for risk stratification in siblings of index cases with T1DM and supports further evaluation of their role in early monitoring strategies.

Background: Cystic fibrosis-related diabetes (CFRD) is a frequent comorbidity in individuals with cystic fibrosis (CF). While insulin secretion defects are the primary mechanism in CFRD pathophysiology, insulin resistance may contribute as an additional risk factor. Early detection of insulin resistance may help identify patients at higher risk for earlier CFRD development. Objective: The aim of this study was to evaluate the ability of the Matsuda Index to identify insulin resistance in pediatric CF patients and to compare it with HOMA-IR as complementary indicators of glucose metabolism. Methods: In this cross-sectional study, fifty children with CF aged 6–16 years were included. The study involved measuring anthropometric data, fasting insulin, fasting glucose levels, glycated hemoglobin (HbA1c), and C-peptide. An assessment of glucose and insulin levels was performed on the patients through an oral glucose tolerance test (OGTT) at 0, 60, and 120 min. The Matsuda Index was computed, wherein a threshold of ≤4.5 signifies the presence of insulin resistance. Statistical analyses were conducted to compare insulin resistance and sensitivity across groups, using t-tests, correlation, and ANOVA. Results: Among the 50 observed patients, the average Matsuda index score was 17.08 with a standard deviation of 11.16. Eleven individuals (22%) exhibited insulin resistance with a Matsuda Index ≤ 4.5. These patients showed significantly higher insulin levels at 60 and 120 min during the OGTT, with statistically significant p-values of 0.008 and 0.002, respectively. Conclusions: The Matsuda Index may serve as a useful adjunctive tool to help identify insulin resistance in pediatric CF patients, particularly during puberty. Early detection of insulin resistance through the Matsuda Index may facilitate risk stratification and enable timely interventions that could potentially delay the onset or progression of CFRD. However, it should be noted that the ≤4.5 cut-off value was derived from adult studies, and its validity in pediatric CF populations has not been established, which represents a limitation of our finding.

Biochemical-Clinical Characteristics of Biotin and Possible Evolutionary Insights on the Place of Its in the Origin of life and the Metabolic Organization - Inherited Metabolic Disorders and Nutrition

This study aimed to evaluate the prevalence of metabolic syndrome (MetS) in children with Type 1 Diabetes Mellitus (T1DM) and to determine the predictive value of simple anthropometric measurements-particularly neck circumference (NC) and waist circumference (WC)-in identifying MetS. A total of 168 children (aged 6-18 years) with T1DM were included in this cross-sectional study. Anthropometric (NC, WC, BMI, TMI) and laboratory parameters (lipid profile, HbA1c) were recorded. MetS diagnosis was established according to the International Diabetes Federation (IDF) criteria. Receiver operating characteristic (ROC) curve analysis and LASSO regression were employed to identify key predictors. The prevalence of MetS was 8.9%. Children with MetS had significantly higher BMI, WC, NC, HC, and TMI values compared to non-MetS counterparts. ROC analysis revealed WC z-score had the highest discriminative power (AUC: 0.954), followed by NC z-score (AUC: 0.906). LASSO regression identified NC z-score and BMI percentile as the most robust predictors. A strong positive correlation was observed between NC and WC (r = 0.812, p 1.04 or WC z >1.41 as actionable thresholds.

Background: Although there a well‐known correlation in genotype and phenotype, patients with 21‐OHD caused by severe pathogenic variants have better correlation, whereas inconsistencies are more common in the presence of milder variants. This study aimed to evaluate CYP21A2 genotyping and reveal the genotype–phenotype correlation in children diagnosed with 21‐OHD in the South‐eastern Anatolia region, where ethnic diversity and consanguineous marriage rates are high.Methods: The patients were divided into three groups: salt wasting (SW), simple virilizing (SV) and non‐classical (NC). Pathogenic variants of the CYP21A2 gene were classified into six groups based on predicted 21‐hydroxylase activity: null‐A‐B‐C‐D‐E. CYP21A2 genotyping was performed by sequence‐specific primer and sequenced with next generation sequencing (NGS), and the expected phenotypes were compared to the observed phenotypes.Results: The overall genotype–phenotype concordance was found to be 73.1% (68/93). The expected concordance with the SW form of the null (n = 12) and A (n = 51) groups is 91.6% and 88.2%, respectively. While the percentage of the expected clinical form of SV in patients in group B (n = 5) was 80%, the concordance for the expected clinical form of NC for group C (n = 25) was not strong enough (32%).Conclusion: This study demonstrates that children with 21‐hydroxylase deficiency show a good correlation between severe pathogenic variants and predicted clinical phenotypes; however, the correlation is not strong enough between milder variants. The discrepancies could have resulted from the complex characteristics of 21‐OHD genotyping and the limitations of using NGS alone without integrating with other comprehensive methods.

Journal of Clinical Research in Pediatric Endocrinology

Objectives: Human recombinant enzyme replacement therapy, given to compensate for genetic enzyme deficiency in lysosomal storage diseases, delays the progression of the disease and improves the quality of life. However, enzyme replacement therapy may cause hypersensitivity reactions. Within the scope of this research, we aimed to elucidate the frequency and clinical features of hypersensitivity reactions against enzyme replacement therapy in children with lysosomal storage diseases and clarify the management of these reactions. Methods: Medical records of pediatric patients with lysosomal storage disease and receiving enzyme replacement therapy were retrospectively reviewed, and patients who experienced allergic reactions were included in the study. The demographic characteristics of the patients, their diagnosis, the responsible enzyme, the time at which the reaction started and at what dose, the signs and symptoms associated with the reaction, diagnostic tests, the management of the reaction, and the protocol applied for the maintenance of enzyme replacement therapy after the reaction were recorded. Results: Hypersensitivity reactions developed in 18 of 71 patients (25.3 %) who received enzyme replacement therapy. The most common cutaneous findings were observed. Anaphylaxis developed in 6 of 18 patients. Patients who experienced recurrent hypersensitivity reactions with premedication or a slower infusion rate, those with positive skin test results, and patients who developed anaphylaxis were given enzyme replacement therapy with desensitization. Conclusions: HSR may develop during enzyme replacement therapy, which are vital in lysosomal storage diseases, and discontinuation of enzyme replacement therapy is a significant loss for patients with metabolic disorders. These reactions can be treated with premedication and long-term infusions, but some patients may require desensitization protocols for continued treatment.