Triglyceride glucose index is superior biomarker for predicting type 2 diabetes mellitus in children and adolescents.

The triglyceride-glucose (TyG) index is associated with predicting type 2 diabetes mellitus (T2DM), but its relationship with homeostatic model assessment of insulin resistance (HOMA-IR) in T2DM is not established. We aimed to investigate the role of TyG index for detection of T2DM in children and adolescents and compare it with HOMA-IR. A cross sectional study was performed in 176 overweight or obese children and adolescents with mean age of 11.34 ± 3.24 years. TyG index was calculated as ln (fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2). Of a total of 176 subjects, 57 (32%) were diagnosed with T2DM. Significant differences were observed in the TyG index between T2DM and non-T2DM (p < 0.001). The TyG index had a positive correlation with fasting glucose (r = 0.519, p < 0.001), HOMA-IR (r = 0.189, p < 0.017), HbA1c (r = 0.429, p < 0.001), total cholesterol (TC) (r = 0.257, p = 0.001), TG (r = 0.759, p < 0.001), and low-density lipoprotein cholesterol (LDL-C)(r = 0.152, p < 0.001), and a negative correlation with high-density lipoprotein cholesterol (HDL-C)(r = -0.107, p < 0.001) after controlling for sex, age and BMI standard deviation scores (SDS). In multiple regression analyses, 91.8% of the variance in TyG index was explained by age, glucose, HOMA-IR, TG, LDL-C, and HDL-C (p < 0.001). In the receiver operating characteristic (ROC) analysis, the TyG index [area under the curve (AUC) 0.839)] showed a better performance compared to HOMA-IR (AUC 0.645) in identifying patients with T2DM (p < 0.001). In conclusion, the TyG index had significant association with insulin resistance in T2DM and was superior to HOMA-IR in predicting T2DM in children and adolescents.

Mild Phenotype of Xq Deletion and 3q Duplication Associated with der(X)t(X;3)(q21.1;q22.1) without Loss of XIST Gene.

We report a 10-year-old female patient with der(X)t(X;3)(q21.1;q22.1), resulting in 3q duplication and Xq deletion. The main clinical feature was primary ovarian failure and there was no abnormal phenotype corresponding to 3q duplication syndrome. This might be explained by the XIST gene at the X-inactivation center on Xq13.2, which was not deleted in this case. The conventional karyotyping was preliminarily reported as 46,X,inv(X) (q13q26) due to the similar banding patterns of Xq13.2-q24 and 3q25.33-q29. This case highlights the value of using a chromosomal microarray as a clinical diagnostic test for individuals with developmental delay or congenital anomalies.

Gene polymorphisms in leptin and its receptor and the response to growth hormone treatment in patients with idiopathic growth hormone deficiency.

This study aimed to investigate the relationships between genetic polymorphisms of leptin/receptor genes and clinical/biochemical characteristics in children with growth hormone deficiency (GHD). Ninety-three GHD children and 69 age-matched normal controls were enrolled. Anthropometric measurements, bone age, and laboratory test results were obtained. Polymorphisms in the LEP gene promoter locus (LEP-2548, rs7799039) and LEPR genes (K109R, rs1137100 and Q223R, rs1137101) were analyzed using PCR-RFLP. The serum leptin levels were measured using an ELISA kit. The median height and BMI z-scores of all GHD subjects were -2.20 and -0.26, respectively, and those of normal controls were -0.30 and -0.13, respectively. The serum leptin levels were similar between GHD subjects and normal controls (p = 0.537), but those were different between the complete GHD (6.97 ng/mL) and partial GHD (4.22 ng/mL) groups (p = 0.047). There were no differences in the genotypic distributions of LEP-2548, LEPR K109R, and Q223R between GHD subjects and normal controls. However, GHD subjects with the G allele at LEP-2548 showed higher IGF-1 (p = 0.047) and IGFBP-3 SDSs (p = 0.027) than GHD subjects with the A allele. GHD subjects with the G allele at LEPR Q223R showed lower stimulated GH levels (p = 0.023) and greater height gain after 1 year of GH treatment (p = 0.034) than GHD subjects with the A allele. In conclusion, leptin/leptin receptor genes are suggested to have the role of growth-related factors, which can affect various growth responses in children who share the same disease entity.

Inhibin B as a screening tool for early detection and treatment monitoring of central precocious puberty.

Anti-Müllerian hormone (AMH) and inhibin B are considered possible biomarkers of central precocious puberty (CPP). The aim of this study was to evaluate serum levels of AMH and inhibin B, to investigate their regulatory patterns, and to study their clinical significance in girls with CPP. In total, 48 girls with CPP and 35 age-matched prepubertal control girls were enrolled in the study. AMH and inhibin B levels were determined in the CPP and control groups. In the patient group, AMH and inhibin B levels were evaluated during 1 year of gonadotropin releasing hormone analog (GnRHa) treatment. The mean inhibin B level in the CPP group was significantly higher than that in the control. AMH levels were not different between the two groups. After GnRHa treatment. AMH and inhibin B levels decreased significantly. Based on the ROC analysis, the cutoff value for inhibin B to determine CPP was 19.59 pg/mL, with 83.3% sensitivity and 82.9% specificity, and the area under the curve was 0. 852. Inhibin B was useful for determining CPP and the therapeutic effects of GnRHa treatment in girls with CPP. AMH interacted, in part, with the hypothalamo-pituitary gonadal axis, but its clinical implications in CPP should be further investigated.

Random urinary gonadotropins as a useful initial test for girls with central precocious puberty.

Recent evidence indicates that urinary gonadotropins may be an alternative method for detecting pubertal disorders. The aim of this study was to evaluate the associations of first morning voided (FMV) and random urinary gonadotropins with the pubertal response to a gonadotropin-releasing hormone (GnRH) stimulation test to determine whether random urinary gonadotropins can be used as an alternative method for evaluating central precocious puberty (CPP). In total, 100 girls aged 6.0-8.9 years were enrolled. The subjects were divided into two groups according to their pubertal response to the GnRH stimulation test: a positive group (n = 68) and a negative group (n = 32). Random urinary luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the LH:FSH ratio were significantly positively correlated with FMV urinary LH (r = 0.411, p < 0.001), FMV urinary FSH (r = 0.494, p < 0.001), and the FMV urinary LH:FSH ratio (r = 0.519, p < 0.001). The optimal cutoff values from receiver operating characteristic (ROC) curve analyses were determined to be 0.20 IU/L for random urinary LH (area under the curve (AUC) of 0.812, p < 0.001), 3.03 IU/L for random urinary FSH (AUC of 0.670, p = 0.004) and 0.08 for the random urinary LH:FSH ratio (AUC of 0.784, p < 0.001). No differences were observed between FMV and random urinary LH (p = 0.827), between FMV and random urinary FSH (p = 0.650), or between the FMV and random urinary LH:FSH ratio (p = 0.688) in ROC curve analyses with DeLong's test. Based on our findings, random urinary gonadotropins may be applicable in clinical practice as a useful initial test for girls with CPP.

Serum Makorin ring finger protein 3 values for predicting Central precocious puberty in girls.

This study evaluated the serum level of MKRN3 and investigated its diagnostic usefulness in girls with central precocious puberty (CPP). In total, 41 girls with CPP and 35 age-matched normal control girls were enrolled. Serum values of MKRN3 were measured in both groups. Gonadotropin and estradiol concentrations were evaluated after 6 and 12 months of GnRH agonist (GnRHa) treatment in CPP patients. The MKRN3 concentrations were much lower in the patient group than in the control group (p = .005). Over 1 year of GnRHa treatment in patients, the gonadotropin concentrations were significantly decreased (p < .05), while the MKRN3 concentrations were unchanged (p > .05). MKRN3 levels were inversely correlated to standard deviation (SD) in height (r = -0.46, p = .000), SD in weight (r = -0.32, p = .005), Tanner stage (r = -0.41, p = .000), and bone age (r = -0.46, p = .000). Based on ROC analysis, the area under curve was 0.758 for MKRN3, with 82.9% sensitivity and 68.5% specificity. The measurement of serum MKRN3 level may provide some help for CPP prediction, but relatively various values need further validation.

Irisin is a biomarker for metabolic syndrome in prepubertal children.

The aim of the present study was to evaluate the association of irisin with obesity and metabolic syndrome (MetS) in Korean prepubertal children. A total of 96 children and adolescents aged 6 to 10 years (56 males) were included in this study. Subjects were divided into 3 groups: normal weight (n = 54), overweight (n = 16), and obese (n = 26). In the subgroup analyses, overweight/obese children were further divided based on their MetS status (with MetS vs. without MetS). Children with obesity tended to exhibit a lower mean irisin concentration compared to those with normal weight (p = 0.028). Using Pearson's correlation coefficient to compare all the children in the study, there was a significant inverse correlation between irisin and body mass index (BMI) standard deviation scores (SDS) (r = -0.210, p = 0.041), waist circumference SDS (r = -0.203, p = 0.049), and glucose (r = -0.296, p = 0.004). In the subgroup analyses of overweight/obese children, irisin exhibited a significant inverse correlation with glucose (r = -0.507, p = 0.001) and triglycerides (r = -0.331, p = 0.033). Children with MetS exhibited lower irisin concentrations than those without MetS (14.70 ng/mL vs. 22.02 ng/mL, p = 0.001), and these associations were significant after adjusting for age, gender, and BMI SDS (14.51 ng/mL vs. 22.06 ng/mL, p = 0.002). The irisin level of 15.43 ng/mL was determined to be a possible cutoff to distinguish children with metabolic syndrome from overweight/obese children, with a sensitivity of 75% and a specificity of 94% (p < 0.001). Our results suggest that decreased irisin levels may be associated with MetS in prepubertal children and that irisin might be a biomarker for MetS in prepubertal children.

The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty.

This study investigated the relationships of circulating leptin, kisspeptin, and neurokinin B (NKB) levels with precocious puberty (PP) in overweight/obese girls and evaluated the usefulness of these markers in the initiation of puberty. One hundred and twenty-eight girls aged 7.0-8.9 years with PP (group A, normal-weight; group B, overweight/obese) and 30 age-matched normal controls (NC) were enrolled. Serum levels of leptin, kisspeptin, and NKB were measured by commercial kits. Serum leptin levels were higher in group A (4.21 ng/mL) and B (5.64 ng/mL) compared to the NC (2.35 ng/mL, p < .001). Serum kisspeptin levels were lower in group A (0.59 ng/mL) than in group B (0.66 ng/mL, p = .018). Serum NKB levels were not different among the three groups. The predictive value of leptin (AUC =0.791) was lower than that of IGF-1 (AUC =0.917, p = .009), although both were significant markers for PP in the regression analysis. BMI z-score (AUC =0.806) was a predictive factor of PP. In conclusion, a higher level of leptin, IGF-1, and fatness in overweight/obese girls with PP compared to the NC confirms their roles in the regulation of puberty. Further research is needed if the effects of kisspeptin and NKB on puberty are limited at the levels of neurons or target tissue.

High neutrophil : lymphocyte ratio is associated with refractory Kawasaki disease.

BACKGROUND: The clinical significance of the neutrophil : lymphocyte ratio (NLR) has not yet been fully elucidated in Kawasaki disease (KD). The purpose of this study was to investigate the relationship between NLR and response to i.v. immunoglobulin (IVIG), and its effect on coronary abnormalities in KD. METHODS: A total of 196 KD patients treated with IVIG were analyzed. Baseline NLR was evaluated immediately before IVIG therapy and the patients classified into two groups according to NLR. The clinical data, other inflammatory biomarkers, and coronary complications were also assessed. RESULTS: Kawasaki disease patients with NLR ≥ 5 had a greater incidence of IVIG refractoriness than the NLR < 5 group (31.7% vs 4.3%, P < 0.001), but this was not related to the development of coronary abnormalities. The change in NLR after IVIG (i.e. ΔNLR) was significantly decreased in the coronary abnormality group (2.65 ± 1.88 vs 3.81 ± 2.55, P = 0.042). On multivariate analysis, high NLR and CRP were independent predictors of IVIG refractoriness during the acute phase of KD (P = 0.032 in NLR; P = 0.029 in CRP, respectively). CONCLUSIONS: High NLR was closely associated with resistance to IVIG, but it was not related to the occurrence of coronary abnormalities in KD. Low ΔNLR after IVIG, however, was significantly associated with coronary artery abnormalities.

Low vitamin D levels are associated with both iron deficiency and anemia in children and adolescents.

BACKGROUND: We aimed to examine the association between vitamin D deficiency and anemia in a nationally representative sample of Korean children and adolescents. METHODS: Cross-sectional data on 2526 children and adolescents aged 10-20 years from the Korea National Health and Nutrition Examination Survey-V (2010-2012) were used. Anemia was defined according to specifications of the World Health Organization. Iron deficiency was defined as serum ferritin level of <12 ng/mL and transferrin saturation (TSAT) <16%. RESULTS: The prevalence of vitamin D deficiency in Korean children and adolescents was high especially in female (35.7% vs. 50.9%, P < 0.001). The prevalence of anemia was also higher in female (1.1% vs. 6.8%; P < 0.001). In logistic regression, risk factors for anemia were female sex, old age, post-menarche, low household income, vitamin D deficiency, and iron deficiency. The Odds Ratio for anemia, iron deficiency and iron deficiency anemia (IDA) in subjects with vitamin D deficiency (<15 ng/mL) were 1.81(95% CI, 1.13-2.88), 1.94(95% CI, 1.27-2.97), and 2.26 (95% CI, 1.20-4.24) after controlling for other risk factors. However, after examining the sexes separately, only female subjects showed statistical significance. After further controlling for iron deficiency, the risk of anemia was not significant (P = 0.261). CONCLUSIONS: Vitamin D deficiency is associated with increased risk of anemia, especially iron deficiency anemia, in healthy female children and adolescents. However, the association is attenuated after adjustment for iron deficiency. Further studies are needed to determine whether vitamin D deficiency is the cause of anemia, or bystander of nutritional deficiency which cause iron deficiency.

MicroRNAs as novel biomarkers for the diagnosis and treatment of pediatric diseases.

MicroRNAs (miRNAs) are highly conserved noncoding RNAs that regulate gene expression by silencing or degrading messenger RNAs. Many of the approximately 2,500 miRNAs discovered in humans are known to regulate vital biological processes, including cell differentiation, proliferation, apoptosis, and embryonic tissue development. Aberrant miRNA expression may have pathological and malignant consequences. Therefore, miRNAs have emerged as novel diagnostic markers and potential therapeutic targets for various diseases. Children undergo various stages of growth, development, and maturation between birth and adulthood. It is important to study the role of miRNA expression in normal growth and disease development during these developmental stages. In this mini-review, we discuss the role of miRNAs as diagnostic and prognostic biomarkers in various pediatric diseases.

Triglyceride-glucose-alanine aminotransferase index: A noninvasive serum predictor for identifying the severity of pediatric nonalcoholic fatty liver disease.

We hypothesized that the triglyceride-glucose (TyG)-alanine aminotransferase (ALT) index, which combines the TyG index with ALT, may enhance sensitivity and specificity in detecting the severity of nonalcoholic fatty liver disease (NAFLD). A total of 131 NAFLD patients with a mean age of 11.5 ±â€…2.29 years were enrolled, and severity was assessed by ultrasound fatty liver index (US-FLI) scoring. The TyG-ALT index was defined as ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL] × ALT [IU/L]/2). Multiple linear regression analysis revealed a significant association between the TyG-ALT index and US-FLI (ß = 0.317, P < .001) after controlling for sex, age, and body mass index. The TyG-ALT index showed a more stable and superior ability to detect the severity of NAFLD compared to both ALT and the TyG index. The area under the curve values, listed in the order of ALT, TyG index, and TyG-ALT index, were as follows: 0.737 (P < .001), 0.599 (P = .055), and 0.704 (P < .001) at US-FLI ≥ 4 points; 0.717 (P < .001), 0.720 (P < .001), and 0.775 (P < .001) at US-FLI ≥ 5 points; and 0.689 (P < .05), 0.748 (P < .01), and 0.775 (P < .001) at US-FLI ≥ 6 points. The TyG-ALT index is associated with US-FLI score and superior to both ALT and the TyG index in predicting NAFLD severity. These findings indicate the potential of the TyG-ALT index in the management of pediatric NAFLD progression.

α-Klotho levels in girls with central precocious puberty: potential as a diagnostic and monitoring marker.

Background: Recent studies suggest a link between the Klotho protein, sex hormones, and insulin-like growth factor-1 (IGF-1), indicating that α-Klotho levels may rise during puberty, including in central precocious puberty (CPP) cases. This study aimed to explore α-Klotho levels in girls with CPP to assess its potential as a diagnostic and monitoring tool for this condition. Methods: In total, 139 girls, comprising 82 patients diagnosed with CPP and 57 healthy prepubertal controls, were enrolled in this study. From March 2020 to May 2023, we assessed both α-Klotho levels and clinical parameters. α-Klotho concentrations were measured using an α-Klotho ELISA kit. For the girls with CPP, we additionally analyzed samples taken 6 months after GnRH agonist treatment. Results: α-Klotho levels were higher in the CPP group compared with the control (CPP group: 2529 ± 999 ng/mL; control group: 1802 ± 675 pg/mL) (P < 0.001), and its level modest decreased after 6 months of GnRH agonist treatment (2147± 789 pg/mL) (P < 0.001). The association between α-Klotho and IGF-1 SDS, follicular stimulating hormone and baseline luteinizing hormone was assessed by partial correlation after adjusting for age, BMI SDS (r= 0.416, p= <0.001; r= 0.261, p= 0.005; r= 0.278, p= 0.002), respectively. Receiver operating characteristic curve analysis identified an α-Klotho cut-off differentiating CPP from controls, with a cut-off of 1914 pg/mL distinguishing girls with CPP from controls with a sensitivity of 69.5% and specificity of 70.2%; the area under the curve was 0.723. Conclusion: The findings of our study are the first step towards deciphering the role of α-Klotho in puberty induction. With additional data and further research, α-Klotho could potentially be utilized as a significant diagnostic and monitoring tool for CPP.

Floating-Harbor Syndrome in a Korean Patient with Short Stature and Early Puberty: A Case Report.

Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionately short stature, lack of expressive language, and distinctive facial features, including a large nose, long eyelashes, deeply set eyes, and a triangular face. We present a case of an 11-year-old Korean girl who was initially suspected of having Noonan-like syndrome but was later diagnosed with Floating-Harbor syndrome. The patient exhibited short stature, developmental language delay, dysmorphic facial features, and early puberty. Targeted exome sequencing revealed a heterozygous mutation, c.7303C>T (p.Arg2435Ter), in the SRCAP gene, confirming a diagnosis of Floating-Harbor syndrome. She responded well to human recombinant growth hormone and gonadotropin-releasing hormone (GnRH) agonist, effectively suppressing bone maturation and improving her height SDS from -4.6 to -2.4.

Triglyceride Glucose Index is Associated with Ultrasonographic Fatty Liver Indicator in Children and Adolescents with Non-alcoholic Fatty Liver Disease.

Objective: Non-alcoholic fatty liver disease (NAFLD) is defined as chronic hepatic steatosis and is becoming prevalent along with the increasing trend of obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis (NASH) from simple steatosis. This study evaluates the association between the triglyceride glucose (TyG) index and the ultrasonographic fatty liver indicator (US-FLI), and the possibility of using the TyG index for prediction of severity of pediatric NAFLD. Methods: One hundred twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into 3 groups according to body mass index (BMI). Ninety two were obese, and 19 and 10 were overweight and normal weight, respectively. Results: The homeostatic model assessment for insulin resistance (HOMA-IR) was highest in the group with obesity (P=0.044). The TyG index and US-FLI did not differ significantly among the 3 BMI groups (P=0.186). Fourteen (11.6 %) of the 121 patients had US-FLI  6, in whom the BMI-SDS and TyG index were higher (P=0.017, P=0.004), whereas HOMA-IR did not differ significantly from the group with US-FLI < 6 (P=0.366). US-FLI was associated with BMI-SDS and the TyG index. TyG index was significantly associated with US-FLI after adjustment for BMI-SDS. The cut-off value for the TyG index for predicting US-FLI  6 was 8.91, with an area under the curve of 0.785. Conclusion: TyG index was associated with the degree of hepatic steatosis, suggesting that it might be a useful tool for predicting the severity of pediatric NAFLD.

Usefulness of two-dimensional shear wave elastography in the assessment of non-alcoholic fatty liver disease in children and adolescents.

Two-dimensional shear wave elastography (2D-SWE) evaluates liver stiffness using a non-invasive method, but studies in the paediatric population are rare. This study evaluated the role of 2D-SWE in the diagnosis and severity of paediatric non-alcoholic fatty liver disease (NAFLD). In total, 131 patients with NAFLD and 25 healthy controls were enrolled in this study. The diagnosis and severity of NAFLD were initially assessed using the ultrasound fatty liver index (US-FLI), and all participants underwent 2D-SWE. US-FLI semi-quantitatively measures the severity of NAFLD on a scale of 2-8. The assessment of liver stiffness measurement (LSM) by 2D-SWE is presented in kilopascals (kPa). The NAFLD group was characterised by significantly higher LSM (4.40 ± 0.90 kPa) than the control group (3.76 ± 0.28 kPa) (P < 0.001). 2D-SWE significantly correlated with age, height, weight, body mass index, glucose, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, US-FLI, and triglyceride-glucose index (P < 0.001). In the receiver operating characteristic curve analysis, the area under the curve of LSM for predicting US-FLI ≥ 2 and ≥ 6 was 0.784 (P < 0.001) and 0.819 (P < 0.001), respectively. In conclusion, we suggest that 2D-SWE can be used as a non-invasive diagnostic tool for diagnosing and assessing the severity of paediatric NAFLD.

Influence of catch-up growth on IGFBP-2 levels and association between IGFBP-2 and cardiovascular risk factors in Korean children born SGA.

Small for gestational age (SGA) at birth and postnatal growth pattern may have an impact on insulin resistance and body composition in their later life. Emerging evidence has indicated that insulin-like growth factor binding protein-2 (IGFBP-2) may be related to insulin sensitivity. The aim of this study was to evaluate insulin resistance and IGFBP-2 levels in SGA children, and to identify the effect of catch-up growth on IGFBP-2 concentration. Serum IGFBP-2 levels were measured in 103 Korean SGA children including 49 prepubertal and 54 pubertal subjects. Anthropometric values, fasting serum levels of metabolic parameters and insulin sensitivity indices were determined. Each prepubertal or pubertal group was subgrouped based on height or weight catch-up growth. The subgroups with weight catch-up showed higher values of BMI, body fat mass, percent body fat, and total cholesterol. Particularly in pubertal children, IGFBP-2 concentration was lower in the subgroup with weight catch-up. Catch-up growth in height did not affect insulin resistance and metabolic parameters. IGFBP-2 levels were inversely correlated with BMI, body fat mass, percent body fat, insulin and leptin levels in both prepubertal and pubertal groups. Additionally in the pubertal group, systolic blood pressure, cholesterol levels were related to IGFBP-2. A strong relationship between IGFBP-2, the insulin sensitivity index, and some cardiovascular risk factors was observed in children born SGA, suggesting that IGFBP-2 might be a promising marker for early recognition of insulin resistance, particularly in children with weight catch-up.

Association between insulin-like growth factor binding protein-2 levels and cardiovascular risk factors in Korean children.

Emerging evidence has indicated that insulin-like growth factor binding protein-2 (IGFBP-2) may be involved in the development of obesity and insulin resistance like IGFBP-1. The aim of this study was to measure serum IGFBP-2 levels in overweight and obese children and to compare these levels with those of controls. We also analyzed the associations between IGFBP-2 and insulin sensitivity indices and cardiovascular risk factors. 134 Korean children including 55 overweight and 59 obese subjects were enrolled. We measured anthropometric values and determined fasting serum levels of IGFBP-2, glucose, insulin, lipid profiles, and insulin sensitivity indices including the homeostatic model assessment of insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). The subjects were subgrouped based on body mass index (BMI) and pubertal stage, and association analyses between IGFBP-2 levels and measured factors were performed in each group. Serum IGFBP-2 levels in overweight or obese children were significantly lower than those of controls regardless of pubertal development. Serum IGFBP-2 levels were negatively correlated with weight, BMI, waist circumference, fasting insulin levels, and HOMA-IR but were positively correlated with QUICKI. The associations were stronger in pubertal children than those in prepubertal children. However, no association was observed between serum IGFBP-2 levels and auxological or metabolic parameters in children with normal BMIs. These results suggested that IGFBP-2 might be a promising marker for early recognition of insulin resistance, particularly in overweight or obese children, regardless of pubertal stage.

A Novel Heterozygous ACAN Variant in a Short Patient Born Small for Gestational Age with Recurrent Patellar Dislocation: A Case Report

ACAN variants can manifest as various clinical features, including short stature, advanced bone age (BA), and skeletal defects. Here, we report rare clinical manifestations of ACAN defects in a 9 year, 5 month-old girl born small for gestational age (SGA), who presented with short stature, and was initially diagnosed with idiopathic growth hormone deficiency. She displayed several dysmorphic features, including genu valgum, cubitus valgus, and recurrent patellar dislocations. She presented with progressive advancement of BA compared with chronological age. Whole exome sequencing confirmed the presence of a novel heterozygous nonsense variant, c.1968C>G, p.(Tyr656*), in ACAN. ACAN variants should be considered in short stature patients born SGA with joint problems, particularly those with recurrent patellar dislocation and genu valgum.

Association between uric acid and height during growth hormone therapy in children with idiopathic short stature.

Background: Serum uric acid (UA) within appropriate levels is reported to be beneficial in patients with idiopathic short stature (ISS). This study aimed to evaluate the association between serum UA levels and height standard deviation scores (SDS) in patients with ISS during growth hormone (GH) therapy. Methods: A longitudinal study (LG Growth Study) of 182 children (mean age: 7.29±2.60 years) with ISS was performed. All participants were in the prepubertal stage and treated with GH, and the data within a treatment period of 30 months were analyzed. Results: In the adjusted Pearson's correlation, UA was significantly correlated with height SDS after controlling for sex, age, and body mass index (BMI) SDS (r=0.22, p=0.007). In the adjusted multiple regression analyses, the height SDS was significantly associated with UA after controlling for sex, age, and BMI SDS (ß=0.168, p=0.007). Within the 30-month treatment period, the UA levels significantly increased as the height SDS increased, and the mean UA levels at baseline and 30 months after treatment were 3.90±0.64 mg/dL and 4.71±0.77 mg/dL, respectively (p=0.007). Discussion: In conclusion, UA is related to height SDS, and GH treatment leads to a significant increase in UA without hyperuricemia. Elevated UA is considered a favorable outcome of GH therapy, and further studies are needed to determine its role as a monitoring tool.