Jin Soon Hwang

Bone mineral density according to age, bone age, and pubertal stages in korean children and adolescents.

To determine whether bone age (BA)-based bone mineral density (BMD) reference values are more accurate than chronological age-based BMD values in predicting the BMD of children who have a discrepancy between their chronological age and BA; we calculated BMD reference values for 514 healthy Korean children (262 girls and 252 boys) aged 5-20yr by dual-energy X-ray absorptiometry. We found that children with BA chronological age discrepancy fitted better to the BA BMD reference curve than to the chronological age BMD reference curve. In contrast, most children without BA-chronological age discrepancy fitted well to both BA and chronological age BMD reference curves, because the 2 reference curves are very similar. In the linear regression analysis, BA-based equations for BMD had a higher R(2) value and lower standard error of estimate than chronological age-based equations. These results indicate that BA-based BMD values are more accurate in predicting BMD in children who have a discrepancy between their BA and chronological age.

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.

Serum Lipid Concentrations, Prevalence of Dyslipidemia, and Percentage Eligible for Pharmacological Treatment of Korean Children and Adolescents; Data from the Korea National Health and Nutrition Examination Survey IV (2007–2009)

Objectives Dyslipidemia is one of the important modifiable risk factors for cardiovascular disease. Thus, to know the prevalence of dyslipidemia is the 1st step to make guidelines of screening and management plan. Although, American Academy of Pediatrics updated the guidelines for lipid in childhood, Asian study is rare. Methods The authors aimed to make a reference of each serum lipid level of Korean children and adolescents (2,363 subjects aged 10 to 18 years) from the data of Korea National Health and Nutrition Examination Survey IV (2007–2009). Results The mean serum concentrations for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) were 158 mg/dL, 90 mg/dL, 90 mg/dL, and 49 mg/dL, respectively. The 95th percentile values for TC, LDL-C, and TG were 203 mg/dL, 129 mg/dL, and 185 mg/dL, respectively. The 5th percentile value for HDL-C was 36 mg/dL. The prevalence of hypercholesterolemia, high LDL-C, high TG, and low HDL-C was 6.5%, 4.7%, 10.1%, and 7.1%, respectively. Considering the risk factors such as obesity, hypertension, smoking, and diabetes, approximately 0.41% of the subjects were potentially eligible for pharmacological treatment. Conclusions This information may be useful in not only Korean but also Asian planning programs for the prevention of cardiovascular disease through lipid control from childhood.

Reference values for serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Korean children and adolescents.

OBJECTIVE Measurements of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are utilized in the diagnostic work-up and clinical management of children with growth disorders. We designed this study to establish the reference values of serum IGF-I and IGFBP-3 levels according to age, sex and pubertal stage in Korean children and adolescents. METHODS For the study, 1378 healthy Korean children and adolescents aged 0 to 17 years (722 boys, 656 girls) were randomly selected. Blood samples were collected, and the stored sera were assayed for IGF-I and IGFBP-3 using immunoradiometric assay (IRMA, Immunotech). The R 2.8.1 program (Bell Laboratories) was used to generate reference percentile curves for IGF-I and IGFBP-3 according to age, sex, and pubertal stage RESULTS Serum IGFBP-3 level was higher in girls compared to that in boys of the same ages throughout the pubertal period, whereas IGF-I was only higher for girls younger than 13 years of age. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage, followed by a progressive decline thereafter. Peak levels of serum IGF-I and IGFBP-3 were observed two years earlier in girls compared to those in boys (13 vs. 15 years of age, respectively). Serum IGF-I and IGFBP-3 concentrations were highest at Tanner stage IV in boys and girls, with a subsequent decline. CONCLUSIONS Our reference value model based on age, sex, and pubertal stage can improve the diagnostic utility of IGF-1 and IGFBP-3 levels in the evaluation and management of Korean children and adolescents with growth disorders.

Clinical implications of Nε-(carboxymethyl)lysine, advanced glycation end product, in children and adolescents with type 1 diabetes

Aim:  The aim of this study was to investigate the relationship between serum levels of the glycoxylation product Nε‐(carboxymethyl)lysine (CML) and development of chronic diabetic complications and degree of diabetic control in children and adolescents with type 1 diabetes.

Changes in bone mineral density and body composition in children with central precocious puberty and early puberty before and after one year of treatment with GnRH agonist.

Background/Aims: Much concern has been raised and debated on the effects of obesity and bone mineral density (BMD) after treatment with GnRH agonist. The aim of this study was to assess BMD and body composition, especially percent body fat (%FM) based on dual-energy X-ray absorptiometry (DEXA), before and after 1 year of treatment with GnRH agonist in Korean girls. Methods: We assessed BMD and body composition in 121 Korean girls with precocious puberty before and after 1 year of treatment with GnRH agonist. BMD and body composition values were measured by using DEXA. Results: The BMD standard deviation score of each region of interest for chronological age (CA) were higher than zero, but lower than zero for bone age (BA) at baseline and the gap was decreased after 1 year of GnRH agonist treatment. The fat mass (FM) and %FM for both CA and BA were significantly higher than zero at baseline. After GnRH agonist treatment, FM and %FM decreased for CA, but increased for BA. Conclusion: Pituitary-gonadal axis suppression by GnRH agonist does not reverse the progression of bone mass acquisition and does not increase the prevalence of obesity in Korean children with precocious puberty.

Dilated Cardiomyopathy in a 2 Month-Old Infant: A Severe Form of Hypocalcemia With Vitamin D Deficient Rickets

Dilated cardiomyopathy, which mostly has an idiopathic etiology or is caused by genetic inheritance or infection, can cause irreversible congestive heart failure. Hypocalcemia is a rare etiology of reversible dilated cardiomyopathy. Here we report the case of a two-month-old girl with congestive heart failure who was diagnosed as having dilated cardiomyopathy secondary to hypocalcemia. After calcium and vitamin D replacement therapy, the patient showed a rapid reduction in hypocalcemic tetany and a rapid recovery of left ventricular function. The cause of the hypocalcemia was vitamin D deficient rickets. She was exclusively breast-fed as an infant, and her mother had a vitamin D deficiency and was diagnosed with osteomalacia.

Low Frequency of MKRN3 Mutations in Central Precocious Puberty Among Korean Girls

Mutations of MKRN3, the gene encoding makorin RING-finger protein 3, lead to central precocious puberty (CPP). The aim of this study was to investigate mutations of the MKRN3 gene in Korean girls with CPP. Two hundred-sixty Korean girls with idiopathic CPP were included. Auxological and endocrine parameters were measured, and the entire MKRN3 gene was directly sequenced. MKRN3 gene analysis revealed one novel nonsense mutation (p.Gln281 *) and 6 missense variants (p.Ile100Phe, p.Gly196Val, p.Ile204Thr, p.Gln226Pro, p.Lys233Asn, and p.Ser396Arg). The novel nonsense mutation (p.Gln281 *) was a heterozygous C>T nucleotide change (c.841C>T) predicted to result in a truncated protein due to a premature stop codon in the MKRN3 gene. The nonsense mutation (p.Gln281 *) was only identified in one of the girls and her younger brother. Compared to previous reports on MKRN3 mutations in familial and sporadic cases of CPP, the present study reveals a relatively low number of MKRN 3 mutations in Korean girls with CPP. Larger samples of children with CPP and MKRN3 mutations are necessary in order to clarify whether the clinical course of puberty may differ as compared to idiopathic CPP.

HbA1c and glucose intolerance in obese children and adolescents.

Diabet. Med. 29, e102–e105 (2012)

Response to Growth Hormone Therapy in Children with Noonan Syndrome: Correlation with or without PTPN11 Gene Mutation

Background/Aims: The objective of this study was to evaluate the efficacy of recombinant human growth hormone (rhGH) therapy and the influence of genotype on the response to rhGH therapy in children with Noonan syndrome (NS). Methods: 14 male and 4 female subjects with NS with short stature, whose height was <3rd percentile, were included. The rhGH was subcutaneously administered at a dose of 66 µg/kg/day. Mutations in the PTPN11 gene were identified in 10 subjects (55.6%). Mutations in the SOS1 (2 children, 11.1%), MEK1 (1 child, 5.6%) and KRAS (1 child, 5.6%) genes were also found. Results: Height SDS increased from –2.8 ± 0.9 at the start of rhGH therapy to –2.0 ± 0.9 12 months later (p < 0.001). Height velocity increased from 5.0 ± 0.9 cm/year in the year before treatment to 8.9 ± 1.6 during treatment (p < 0.001). Changes in height SDS, height velocity, and serum IGF-1 level did not differ significantly between those children with or without PTPN11 mutations. Conclusion: The rhGH therapy significantly improved the growth velocity and increased the serum IGF-1 level. Long-term correlation between genotype and rhGH therapy responsiveness needs to be addressed in a large population.