Siblings With Familial Dwarfism Presenting With Acute Myocardial Infarction at Adolescence.

We encountered siblings with familial Majewski osteodysplastic primordial dwarfism type II (MOPD II) with acute myocardial infarction in adolescence and in their early 20s. We successfully performed percutaneous and surgical coronary interventions. From these cases, we were able to better understand coronary artery disease of MOPD II and provide better management. (Level of Difficulty: Intermediate.).

Clinical Application of Sequential Epigenetic Analysis for Diagnosis of Silver-Russell Syndrome.

BACKGROUND: Silver-Russell syndrome (SRS) is a pre- or post-natal growth retardation disorder caused by (epi)genetic alterations. We evaluated the molecular basis and clinical value of sequential epigenetic analysis in pediatric patients with SRS. METHODS: Twenty-eight patients who met≥3 Netchine-Harbison clinical scoring system (NH-CSS) criteria for SRS were enrolled;26 (92.9%) were born small for gestational age, and 25 (89.3%) showed postnatal growth failure. Relative macrocephaly, body asymmetry, and feeding difficulty were noted in 18 (64.3%), 13 (46.4%), and 9 (32.1%) patients, respectively. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) on chromosome 11p15 was performed as the first diagnostic step. Subsequently, bisulfite pyrosequencing (BP) for imprinting center 1 and 2 (IC1 and IC2) at chromosome 11p15, MEST on chromosome 7q32.2, and MEG3 on chromosome 14q32.2 was performed. RESULTS: . Seventeen (60.7%) patients exhibited methylation defects, including loss of IC1 methylation (N=14; 11 detected by MS-MLPA and three detected by BP) and maternal uniparental disomy 7 (N=3). The diagnostic yield was comparable between patients who met three or four of the NH-CSS criteria (53.8% vs 50.0%). Patients with methylation defects responded better to growth hormone treatment. CONCLUSIONS: NH-CSS is a powerful tool for SRS screening. However, in practice, genetic analysis should be considered even in patients with a low NH-CSS score. BP analysis detected additional methylation defects that were missed by MS-MLPA and might be considered as a first-line diagnostic tool for SRS.

Cardiac autonomic dysfunction is associated with hypothalamic damage in patients with childhood-onset craniopharyngioma.

BACKGROUND: Autonomic nervous system dysfunction is implicated in the development of hypothalamic obesity. We investigated the relationship between hypothalamic involvement (HI), central obesity, and cardiac autonomic dysfunction by assessing heart rate variability (HRV) indices in patients with childhood-onset craniopharyngioma. METHODS: A cross-sectional study of 48 patients (28 males, 10-30 years old) with hypothalamic damage after childhood-onset craniopharyngioma was performed. Postoperative HI was graded as mild (n = 19) or extensive (n = 29) on magnetic resonance imaging. Anthropometry, body composition and HRV indices including the standard deviation of all normal R-R intervals (SDNN) and total power (TP) as overall variability markers, root-mean square differences of successive R-R intervals (RMSSD) and high frequency (HF) as parasympathetic modulation markers, and low frequency (LF) as a sympathetic/sympathovagal modulation marker were measured. RESULTS: Patients with extensive HI had increased means of body mass index, waist circumference, and fat mass than those with mild HI (P < 0.05, for all). Centrally obese patients had a lower mean HF, a parasympathetic modulation marker, than centrally non-obese patients (P < 0.05). The extensive HI group had lower means of overall variability (SDNN and TP), parasympathetic modulation (HF), and sympathetic/sympathovagal modulation (LF) than the mild HI group (P < 0.05, for all). The interaction effect of HI and central obesity on HRV indices was not significant. In models adjusted for age, sex, and family history of cardiometabolic disease, the means of the overall variability indices (P < 0.05 for both SDNN and TP) and a sympathetic/sympathovagal modulation index (P < 0.05 for LF) were lower with extensive HI, without differences according to central obesity. CONCLUSIONS: The reduced HRV indices with extensive HI suggests that hypothalamic damage may contribute to cardiac autonomic dysfunction, underscoring the importance of minimizing hypothalamic damage in patients with childhood-onset craniopharyngioma.

History of insulin treatment of pediatric patients with diabetes in Korea.

The year 2021 is the centennial of insulin discovery. The discovery of insulin changes diabetes mellitus from a death sentence to a manageable disease. It became a historical turning point in the lives of people with diabetes. Since the first use of insulin in a patient in 1922, insulin and its analogs have been remarkable in saving the lives of people with diabetes. As insulin began to be used as a drug, it was introduced to, and used in Korea until now. This review briefly summarizes the history of insulin treatment in Korean children and adolescents with diabetes.

Clinical and Molecular Characteristics of GNAS Inactivation Disorders Observed in 18 Korean Patients.

BACKGROUND: The GNAS gene on chromosome 20q13.3 is a complex, imprinted locus regulated in a tissue-specific manner. GNAS inactivation disorders are a heterogeneous group of rare disorders caused by mutations and methylation defects. These are divided into pseudohypoparathyroidism (PHP) types 1A and 1B, pseudo-pseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH), depending on the presence or absence of hormone resistance, Albright's hereditary osteodystrophy (AHO), and ectopic ossification. METHODS: This study analyzed the clinical characteristics and molecular genetic backgrounds of 18 Korean patients from 16 families with a genetically confirmed GNAS defect. Auxological parameters, AHO phenotypes, types of hormonal resistance, family history, and molecular genetic disturbances were reviewed retrospectively. RESULTS: Nine (90%) patients with PHP1A showed resistance to parathyroid hormone (PTH) and all patients showed elevated thyroid-stimulating hormone (TSH) levels at diagnosis. Eight (80%) patients were managed with levothyroxine supplementation. Three of six patients with PHP1B had elevated TSH levels, but none of whom needed levothyroxine medication. AHO features were absent in PHP1B. Patients with PPHP and POH did not show any hormone resistance, and both of them were born as small for gestational age. Among the 11 families with PHP1A, PPHP, and POH, eight different (three novel) mutations in the GNAS gene were identified. Among the six patients with PHP1B, two were sporadic cases and four showed isolated loss of methylation at GNAS A/B:TSS-DMR. CONCLUSIONS: Clinical and molecular characteristics of Korean patients with GNAS inactivation disorders were described in this study. Also, we reaffirmed heterogeneity of PHP, contributing to further accumulation and expansion of current knowledge of this complex disease.

Changes in Adrenal Androgens and Steroidogenic Enzyme Activities From Ages 2, 4, to 6 Years: A Prospective Cohort Study.

CONTEXT: The levels of adrenal androgens are increased through the action of steroidogenic enzymes with morphological changes in the adrenal zona reticularis. OBJECTIVE: We investigated longitudinal changes in androgen levels and steroidogenic enzyme activities during early childhood. DESIGN AND PARTICIPANTS: From a prospective children's cohort, the Environment and Development of Children cohort, 114 boys and 86 girls with available blood samples from ages 2, 4, and 6 years were included. OUTCOME MEASUREMENTS: Serum concentrations of adrenal androgens using liquid chromatography-tandem mass spectrometry and steroidogenic enzyme activity calculated by the precursor/product ratio. RESULTS: During ages 2 to 4 years, 17,20-lyase and dehydroepiandrosterone (DHEA) sulfotransferase activities increased (P < 0.01 for both in boys). During ages 4 to 6 years, 17,20-lyase activity persistently increased, but 3ß-hydroxysteroid dehydrogenase (HSD) and 17ß-HSD activities decreased (P < 0.01 for all). Serum DHEA sulfate (DHEA-S) levels persistently increased from 2, 4, to 6 years, and DHEA, 17-hydroxyprogesterone, and androstenedione levels increased during ages 4 to 6 years (P < 0.01 for all). Serum DHEA-S levels during early childhood were associated with body mass index z-scores (P = 0.001 in only boys). CONCLUSION: This study supports in vivo human evidence of increased 17,20-lyase and DHEA sulfotransferase activities and decreased 3ß-HSD activity during early childhood.

Autonomic Dysfunction is Associated with Increased Cardiometabolic Risk in Patients with Childhood-Onset Craniopharyngioma.

Patients with craniopharyngioma are susceptible to autonomic dysfunction as a result of hypothalamic damage. We evaluated indices of heart rate variability (HRV) in patients with childhood-onset craniopharyngioma to investigate autonomic function and its relationship with components of the metabolic syndrome (MetS). This cross-sectional, case-only study included 53 patients (10-30 years of age). We measured the standard deviation of all normal R-R intervals (SDNN) and total power indicating overall HRV, the root-mean square of the difference of successive R-R intervals (RMSSD) and high frequency indicating parasympathetic modulation, and low frequency. These indices were compared according to the presence of the MetS. During the mean 10.8 years of follow-up, 25% of patients were diagnosed with the MetS. Patients with the MetS showed significantly lower levels of SDNN (29.0 vs. 40.6 ms), total power (416.1 vs. 1129.6 ms2), RMSSD (20.1 vs. 34.5 ms), high frequency (94.7 vs. 338.5 ms2), and low frequency (94.5 vs. 289.4 ms2) than those without (p <0.05, for all). Individual components of the MetS including insulin resistance, serum triglycerides levels, and systolic blood pressure were inversely associated with SDNN, total power, RMSSD and high frequency. Higher overall variability and parasympathetic modulation were related to decreased odds ratios for having the MetS (OR 0.91, p=0.029 for SDNN; OR 0.91, p=0.032 for total power). In conclusion, autonomic dysfunction, as evidenced by reduced HRV indices, is associated with increased cardiometabolic risk in patients with childhood-onset craniopharyngioma.

Arterial stiffness in young women with Turner syndrome using cardio-ankle vascular index.

PURPOSE: Patients with Turner syndrome (TS) have increased risk of morbidities and mortality related to cardiovascular complications. Cardio-ankle vascular index (CAVI) is a novel method of evaluating arterial stiffness independent of changes in blood pressure. We compared arterial stiffness using CAVI between TS patients and healthy control subjects. METHODS: Nineteen young women with TS (mean, 26.8 years; range, 20.0-35.1 years) and 23 healthy women matched for age and body mass index (BMI) were recruited for CAVI measurements at Seoul National University Hospital between 2010 and 2013. Anthropometric parameters, fasting blood testing and measurements of CAVI were compared between the 2 groups. RESULTS: TS patients were significantly shorter (mean: 150.1 cm vs. 160.7 cm, P<0.001) and had lower body weight (mean: 47.0 kg vs. 55.5 kg, P=0.014) than healthy controls, without difference in BMI. CAVI (6.5±0.6 vs. 6.1±0.6, P=0.039) was significantly higher in TS patients compared to healthy controls. Age was positively associated with CAVI (r=0.403, P=0.008) in univariate analysis. After adjusting for age, TS was associated with CAVI (P=0.006). CONCLUSION: Young women with TS showed increased arterial stiffness measured by CAVI compared to healthy women after adjusting for age, suggesting inherent vasculopathy in TS patients.

Cardiac autonomic neuropathy in nonobese young adults with type 1 diabetes.

PURPOSE: The aim of this study was to evaluate the prevalence and risk factors for cardiac autonomic neuropathy (CAN) in nonobese nonobese young type 1 diabetes mellitus (T1DM) patients without micro- or macrovascular complications. METHODS: CAN was assessed in 95 patients with T1DM, aged 18-29 years, using standard cardiovascular reflex tests - heart rate response to deep breathing, standing, and the Valsalva maneuver and blood pressure response to standing. Furthermore, power spectral analyses of overall heart rate variability (HRV), standard deviation of NN intervals (SDNN), and total power (TP) were tested with DiCAN. CAN was defined as abnormal results for at least 1 of the 4 cardiovascular reflex tests. RESULTS: The prevalence of CAN was 12.6%. The frequency of one and 2 abnormal reflex tests was 10.5% and 2.1%, respectively. No significant differences were observed in age, sex, mean hemoglobin A1c (HbA1c) level, and duration of diabetes with respect to presence of CAN. Patients with CAN exhibited lower overall HRV parameters (SDNN and TP) compared with those without CAN even though there was no statistical significance. In multivariable analyses, higher mean HbA1c level was significantly associated with lower overall HRV (ß=-44.42, P=0.002 for SDNN and ß=-2.82, P<0.001 for TP). CONCLUSION: CAN can be detected in 12.6% of young adult T1DM patients even without other micro- or macrovascular complications. Glycemic control is the main determinant to maintain overall HRV and prevent CAN.

How can the occurrence of delayed elevation of thyroid stimulating hormone in preterm infants born between 35 and 36 weeks gestation be predicted?

OBJECTIVE: We evaluated frequency and risk factors of delayed TSH elevation (dTSH) and investigated follow-up outcomes in the dTSH group with venous TSH (v-TSH) levels of 6-20 mU/L according to whether late preterm infants born at gestational age (GA) 35-36 weeks had risk factors. METHODS: The medical records of 810 neonates (414 boys) born at Seoul National University Hospital who had a normal neonatal screening test (NST) and underwent the first repeat venous blood test at 10-21 days post birth were reviewed. RESULTS: Seventy-three (9.0%) neonates showed dTSH, defined as a v-TSH level ≥6.0 mU/L, 12 of whom (1.5%) were started on levothyroxine medication. A multivariate-adjusted model indicated that a low birth weight (LBW <2,000 g), a congenital anomaly, and exposure to iodine contrast media (ICM) were significant predictors for dTSH (all p < 0.05). Among these 73 dTSH infants, all 5 infants with TSH levels ≥20 mU/L began levothyroxine medication, and 6 of 16 infants with v-TSH levels of 10-20 mU/L were indicated for levothyroxine, regardless of coexisting risk factors. However, only 1 of 52 infants with v-TSH levels of 6-10 mU/L who had a congenital anomaly was indicated for levothyroxine. All healthy late preterm infants, including LBW and multiple births, with v-TSH levels of 6-10 mU/L exhibited normal thyroid function. CONCLUSIONS: dTSH was detected in 9.0% and levothyroxine was indicated in 1.5% of infants born at GA 35-36 weeks, particularly those with a LBW, a congenital anomaly, or history of ICM exposure. Either levothyroxine or retesting is indicated for late preterm neonates with TSH levels ≥10 mU/L regardless of risk factors. If healthy preterm neonates show v-TSH levels of 6-10 mU/L, a second repeat test may not be necessary; however, further studies are required to set a threshold for retesting.

Relationship between systolic hypertension assessed by 24-hour ambulatory blood pressure monitoring and aortic diameters in young women with Turner syndrome.

OBJECTIVE: Patients with Turner syndrome (TS) are at high risk for cardiovascular morbidity and mortality due to aortic dilation. We evaluated the prevalence of hypertension and its risk factors and investigated the relationship between systolic hypertension and aortic diameter in young patients with TS. DESIGN: Observational, cross-sectional study. PATIENTS AND MEASUREMENTS: Forty-two patients with TS (15-35 years) who had achieved final adult heights underwent 24-h ambulatory blood pressure monitoring (ABPM). Fasting glucose, insulin and lipid profiles were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Echocardiography was performed to evaluate aortic diameters (aortic annulus, aortic root at the sinuses of Valsalva, sinotubular junction and ascending aorta), which were converted into Turner-specific z-scores. RESULTS: Systolic and/or diastolic hypertension was identified in 71.4% (n = 30) of patients, as assessed by 24-hour ABPM. Twenty-eight patients (66.7%) were nondippers. Patients with systolic hypertension (n = 8, 19.0%) had a higher weight, waist circumference and HOMA-IR levels than those without hypertension (P < 0.05 for all). After adjusting for covariates, HOMA-IR was independently associated with systolic hypertension (odds ratio 10.1, P = 0.043). After adjusting for age and bicuspid aortic valve, systolic hypertension was independently related to increased aortic diameter at the aortic annulus (ß = 1.064, P = 0.009) and sinotubular junction (ß = 1.124, P = 0.016). CONCLUSIONS: Hypertension is highly prevalent and independently associated with IR in young patients with TS. The significant relationship between systolic hypertension and aortic diameters underscores the importance of BP and IR control.

Discrepancies between Glycosylated Hemoglobin and Fasting Plasma Glucose for Diagnosing Impaired Fasting Glucose and Diabetes Mellitus in Korean Youth and Young Adults.

BACKGROUND: Glycosylated hemoglobin (HbA1c) has been recommended as a diagnostic test for prediabetes and diabetes. Here, we evaluated the level of agreement between diagnoses based on fasting plasma glucose (FPG) versus HbA1c levels and determined optimal HbA1c cutoff values for these diseases in youth and young adults. METHODS: The study included 7,332 subjects (n=4,129, aged 10 to 19 years in youth group; and n=3,203 aged 20 to 29 years in young adult group) from the 2011 to 2016 Korea National Health and Nutrition Examination Survey. Prediabetes and diabetes were defined as 100 to 125 mg/dL (impaired fasting glucose [IFG]) and ≥126 mg/dL for FPG (diabetes mellitus [DM] by FPG [DMFPG]), and 5.7% to 6.4% and ≥6.5% for HbA1c, respectively. RESULTS: In the youth group, 32.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 72.2% with DMFPG had an HbA1c ≥6.5%. In the young adult group, 27.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 66.6% with DMFPG had an HbA1c ≥6.5%. Kappa coefficients for agreement between the FPG and HbA1c results were 0.12 for the youth group and 0.19 for the young adult group. In receiver operating characteristic curve analysis, the optimal HbA1c cutoff for IFG and DMFPG were 5.6% and 5.9% in youths and 5.5% and 5.8% in young adults, respectively. CONCLUSION: Usefulness of HbA1c for diagnosis of IFG and DMFPG in Koreans aged <30 years remains to be determined due to discrepancies between the results of glucose- and HbA1c-based tests. Additional testing might be warranted at lower HbA1c levels to detect IFG and DMFPG in this age group.

Thyroid dysfunction in patients with childhood-onset medulloblastoma or primitive neuroectodermal tumor.

PURPOSE: We investigated the clinical characteristics of patients who developed thyroid dysfunction and evaluated the risk factors for hypothyroidism following radiotherapy and chemotherapy in pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). METHODS: The medical records of 66 patients (42 males) treated for medulloblastoma (n=56) or PNET (n=10) in childhood between January 2000 and December 2014 at Seoul National University Children's Hospital were retrospectively reviewed. A total of 21 patients (18 high-risk medulloblastoma and 3 PNET) underwent high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR). RESULTS: During the median 7.6 years of follow-up, 49 patients (74%) developed transient (n=12) or permanent (n=37) hypothyroidism at a median 3.8 years of follow-up (2.9-4.6 years). Younger age (<5 years) at radiation exposure (P=0.014 vs. ≥9 years) and HDCT (P=0.042) were significantly predictive for hypothyroidism based on log-rank test. However, sex, type of tumor, and dose of craniospinal irradiation (less vs. more than 23.4 Gy) were not significant predictors. Cox proportional hazard model showed that both younger age (<5 years) at radiation exposure (hazard ratio [HR], 3.1; vs. ≥9 years; P=0.004) and HDCT (HR, 2.4; P=0.010) were significant predictors of hypothyroidism. CONCLUSION: Three-quarters of patients with pediatric medulloblastoma or PNET showed thyroid dysfunction, and over half had permanent thyroid dysfunction. Thus, frequent monitoring of thyroid function is mandatory in all patients treated for medulloblastoma or PNET, especially, in very young patients and/or high-risk patients recommended for HDCT/ASCR.

The 2017 Korean National Growth Charts for children and adolescents: development, improvement, and prospects.

Growth charts are curves or tables that facilitate the visualization of anthropometric parameters, and are widely used as an important indicator when evaluating the growth status of children and adolescents. The latest version of the Korean National Growth Charts released in 2007 has raised concerns regarding the inclusion of data from both breastfed and formula-fed infants, higher body mass index (BMI) values in boys, and smaller 3rd percentile values in height-for-age charts. Thus, new growth charts have been developed to improve the previous version. The 2006 World Health Organization Child Growth Standards, regarded as the standard for breastfed infants and children, were introduced for children aged 0-35 months. For children and adolescents aged 3-18 years, these new growth charts include height-for-age, weight-for-age, BMI-for-age, weight-for-height, and head circumference-for-age charts, and were developed using data obtained in 1997 and 2005. Data sets and exclusion criteria were applied differently for the development of the different growth charts. BMI-for-age charts were adjusted to decrease the 95th percentile values of BMI. Criteria for obesity were simplified and defined as a BMI of ≥95th percentile for age and sex. The 3rd percentile values for height-for-age charts were also increased. Additional percentile lines (1st and 99th) and growth charts with standard deviation lines were introduced. 2017 Korean National Growth Charts are recommended for the evaluation of body size and growth of Korean children and adolescents for use in clinics and the public health sector in Korea.

Distribution of glycated haemoglobin and its determinants in Korean youth and young adults: a nationwide population-based study.

The present study aimed to describe the distribution of and to investigate the factors associated with glycated haemoglobin (HbA1c) values in Korean youth (10-19 years old) and young adults (20-29 years old). Data from the Korea Health and Nutrition Examination Survey (2011-2015) were used. A total of 6,418 participants (male 3,140 [53.2%]) aged 10-29 years were included in the analysis. Percentiles of HbA1c were calculated and HbA1c values were compared according to age, sex, and associated factors. The mean HbA1c values (% [mmol/mol]) were 5.42 ± 0.01 (35.7 ± 0.1) for youths and 5.32 ± 0.01 (34.7 ± 0.1) for young adults (P < 0.001). Male participants showed significantly higher HbA1c level than females (P < 0.001). When age was grouped into 5-year intervals, HbA1c was the highest in those aged 10-14 years and the lowest in those aged 20-24 years. After controlling for confounding variables, the HbA1c values of youths and male participants were significantly higher than those of young adults and female participants. The present study provides nationally representative data on the distribution of HbA1c values in Korean youth and young adults. There were significant differences in the level of HbA1c according to age and sex.

The serum concentrations of perfluoroalkyl compounds were inversely associated with growth parameters in 2-year old children.

The relationship between the serum concentrations of perfluoroalkyl compounds (PFCs) and growth parameters was investigated in 2-year-old Korean children. The study included 361 children aged 2years (192 boys and 169 girls; 22-27months), born at term appropriate-for-gestational-age, who visited between 2012 and 2013. Growth parameters of height and weight, and serum samples were collected from 2-year-old children. Four PFCs (perfluorohexane sulfonic acid [PFHxS], perfluorooctane sulfonic acid [PFOS], perfluorooctanoic acid [PFOA], and perfluorononanoic acid [PFNA]), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluoroheptanoic acid (PFHpA) were detected in >99, 93.4, 89.8, and 74.2% of the serum samples, respectively. The duration of breastfeeding was positively associated with the serum concentrations of ln-transformed PFHxS, PFOS, PFHpA, PFOA, PFNA, PFDA, and PFUnDA (all P<0.001). Height at 2years of age was inversely related to PFHxS, PFOS, PFOA, PFNA, and PFDA concentrations (adjusted ß per ln unit [95% confidence interval, CI]: -0.84 [-1.26, -0.42], -0.77 [-1.27, -0.15], -0.91 [-1.36, -0.47], -0.48 [-1.40, -0.51], and -0.44 [-0.77, -0.10] cm, respectively), after adjusting for age, sex, and midparental height. Weight at 2years of age was inversely associated with PFNA (adjusted ß per ln unit [95% CI]: -0.32 [-0.48, -0.15] kg), after adjusting for age, sex, and parental BMI. In conclusion, the serum concentrations of PFCs were inversely associated with growth parameters in 2-year-old children.

Association between hemoglobin glycation index and cardiometabolic risk factors in Korean pediatric nondiabetic population.

PURPOSE: The hemoglobin glycation index (HGI) represents the degree of nonenzymatic glycation and has been positively associated with cardiometabolic risk factors (CMRFs) and cardiovascular disease in adults. This study aimed to investigate the association between HGI, components of metabolic syndrome (MS), and alanine aminotransferase (ALT) in a pediatric nondiabetic population. METHODS: Data from 3,885 subjects aged 10-18 years from the Korea National Health and Nutrition Examination Survey (2011-2016) were included. HGI was defined as subtraction of predicted glycated hemoglobin (HbA1c) from measured HbA1c. Participants were divided into 3 groups according to HGI tertile. Components of MS (abdominal obesity, fasting glucose, triglycerides, high-density lipoprotein cholesterol, and blood pressure), and proportion of MS, CMRF clustering (≥2 of MS components), and elevated ALT were compared among the groups. RESULTS: Body mass index (BMI) z-score, obesity, total cholesterol, ALT, abdominal obesity, elevated triglycerides, and CMRF clustering showed increasing HGI trends from lower-to-higher tertiles. Multiple logistic regression analysis showed the upper HGI tertile was associated with elevated triglycerides (odds ratio, 1.65; 95% confidence interval, 1.18-2.30). Multiple linear regression analysis showed HGI level was significantly associated with BMI z-score, HbA1c, triglycerides, and ALT. When stratified by sex, age group, and BMI category, overweight/obese subjects showed linear HGI trends for presence of CMRF clustering and ALT elevation. CONCLUSION: HGI was associated with CMRFs in a Korean pediatric population. High HGI might be an independent risk factor for CMRF clustering and ALT elevation in overweight/obese youth. Further studies are required to establish the clinical relevance of HGI for cardiometabolic health in youth.

Two Korean girls with complete androgen insensitivity syndrome diagnosed in infancy.

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent Müllerian duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

Nonalcoholic fatty liver disease in long-term survivors of childhood-onset craniopharyngioma.

PURPOSE: Hypothalamic obesity in childhood-onset (CO-) craniopharyngioma patients may predispose to nonalcoholic fatty liver disease (NAFLD). This study reviewed the characteristics of NAFLD associated with CO-craniopharyngioma. METHODS: This study retrospectively reviewed 75 patients who underwent surgery for craniopharyngioma while younger than 15 years of age between 2000 and 2016. RESULTS: Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 40 IU/L was observed in 51 of the 75 (68%) CO-craniopharyngioma patients. Imaging studies were performed in 32 patients with elevated liver enzymes. The estimated prevalence of NAFLD in CO-craniopharyngioma was 47%. NAFLD was detected in 22 patients (male 59%, 4.3±4.0 years after first surgery). The mean age at the time of the initial operation was 9.1±2.9 years. Six patients (27.3%) were diagnosed within 1 year. Among the 19 patients with initial height and weight data, the body mass index (BMI) z-score (BMI_Z) at the time of diagnosis with NAFLD was 1.37±1.01 (range, -0.75 to 3.18), with 4 patients (18.2%) being overweight and 9 (40.9%) being obese. BMI_Z increased above BMI_Z at the time of the operation in 13 patients (68.4%). The increment in BMI_Z was 1.13 (range, 0.10-2.84). Seventeen patients did not receive growth hormone. An insulin-like growth factor-I level <3rd percentile was observed in 19 patients. CONCLUSIONS: NAFLD is common in survivors of CO-craniopharyngioma and may develop earlier. If the ALT or AST is above 40 IU/L, a diagnostic work-up should be started.