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.

PurposeAllergic disease and its comorbidities significantly influence the quality of life. Although the comorbidities of allergic diseases are well described in adult populations, little is known about them in preschool children. In the present study, we aimed to assess the prevalence and comorbidity of allergic diseases in Korean preschool children.MethodsWe conducted a cross-sectional study comprising 615 Korean children (age, 3 to 6 years). Symptoms of allergic diseases were assessed using the Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire that was modified for preschool children. Comorbidities of allergic diseases were assessed by 'In the last 12 months, has your child had symptoms?'.ResultsThe prevalence of symptoms of asthma, allergic rhinitis, and atopic dermatitis as recorded using the ISAAC questionnaire, within the last 12 months was 13.8%, 40.7%, and 20.8%, respectively. The symptom rates of allergic conjunctivitis, food allergy, and drug allergy were 14.8%, 10.4%, and 0.8%, respectively. The prevalence of allergic rhinitis in children with asthma was 64.3% and that of asthma in children with allergic rhinitis was 21.6%. The prevalence of rhinitis in children with conjunctivitis was 64.8% and that of conjunctivitis in children with rhinitis was 23.6%.ConclusionThe prevalence of current rhinitis in our preschool children is shown to be higher than that previously reported. Allergic conjunctivitis is closely associated with asthma and allergic rhinitis. However, further studies are warranted to determine the prevalence and effects of these comorbidities on health outcomes in preschool children.

Purpose The triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio has recently been reported as a biomarker of cardiometabolic risk in obese children and adolescents. The purpose of this study is to describe the TG/HDL-C ratio and related factors in overweight and normal weight Korean children and to evaluate whether the high TG/HDL-C ratio is associated with insulin resistance in overweight children and adolescents.MethodsData from 255 overweight (aged 8.7±2.0 years) and 514 normal weight (aged 8.9±1.8 years) children and adolescents were evaluated. Glucose, insulin, total cholesterol (TC), HDL-C and TG levels were measured after overnight fasting, and the TG/HDL-C ratio, non–HDL-C and the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated.ResultsThe TG/HDL-C ratio was higher in overweight group compared to normal weight group (P<0.001). Among overweight children and adolescents, alanine aminotransferase (P=0.018), non–HDL-C (P<0.001), and HOMA-IR (P=0.004) were different between the TG/HDL-C ratio tertile groups. The prevalence of elevated HOMA-IR was increased with increasing TG/HDL-C ratio tertiles (P for trend=0.003). On regression analysis adjusted for age and sex, the BMI (β=0.402, P=0.001) and TG/HDL-C ratio (β=0.251, P=0.014) were independently associated with HOMA-IR (adjusted R2=0.324). The TG/HDL-C ratio of 2.0 or more showed higher sensitivity (55.6%) and specificity (72.9%), when compared to TC (≥200 mg/dL), non–HDL-C (≥145 mg/dL), and LDL-C (≥130 mg/dL) for identifying overweight children with elevated HOMA-IR.ConclusionsThe TG/HDL-C ratio is independently associated with insulin resistance in overweight children and adolescents, and it can be useful in identifying those at higher cardiometabolic risk.

Neonatal hypocalcemia and congenital heart defects has been known as the first clinical manifestation of the chromosome 22q11.2 deletion syndrome (22q11DS). However, because of its wide clinical spectrum, diagnosis of 22q11DS can be delayed in children without classic symptoms. We report the case of a girl with the history of imperforate anus but without neonatal hypocalcemia or major cardiac anomaly, who was diagnosed for 22q11DS at the age of 11 after the onset of overt hypocalcemia. She was born uneventfully from phenotypically normal Korean parents. Imperforate anus and partial cleft palate were found at birth, which were surgically repaired thereafter. There was no history of neonatal hypocalcemia, and karyotyping by GTG banding was normal. At the age of 11, hypocalcemia (serum calcium, 5.0 mg/dL) and decreased parathyroid hormone level (10.8 pg/mL) was noted when she visited our Emergency Department for fever and vomiting. The 22q11DS was suspected because of her mild mental retardation and velopharyngeal insufficiency, and a microdeletion on chromosome 22q11.2 was confirmed by fluorescence in situ hybridization. The 22q11DS should be considered in the differential diagnosis of hypocalcemia at any age because of its wide clinical spectrum.

We evaluated the effects of the timing of treatment initiation with gonadotropin-releasing hormone agonist (GnRHa) on the change in predicted adult height (PAH) in girls with idiopathic true precocious puberty (TPP). Methods: Data for this retrospective study were collected on 104 girls with TPP who were treated with GnRHa for 36 months, between January 2002 and March 2012. Results: The PAH SDS differed before and after treatment in all patients (-1.91 ± 1.47 vs. -1.37 ± 1.17 after 1 year of treatment, -1.96 ± 1.58 vs. -0.48 ± 1.11 after 3 years of treatment) as well as in Group 1 (-2.15 ± 1.54 vs. -1.51 ± 1.20 after 1 year of treatment, -2.09 ± 1.59 vs. -0.55 ± 1.19 after 3 years of treatment) and Group 2 (-1.57 ± 1.34 vs. -1.17 ± 1.12 after 1 year of treatment, -1.50 ± 1.55 vs. -0.21 ± 0.74 after 3 years of treatment). This result could be due to improvement in bone age advancement during the treatment. The difference between mid-parental height SDS and PAH SDS was decreased after GnRHa treatment. However, the means of PAH SDS did not surpass the mid-parental height SDS. Conclusion:GnRHa treatment can preserve growth potential by slowing bone age progression, resulting in short adult height, but it cannot alter the genetic growth potential.

Multiple endocrine neoplasia (MEN) mutation is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. The incidence of insulinoma in MEN is relatively uncommon, and there have been a few cases of MEN manifested with insulinoma as the first symptom in children. We experienced a 9-year-old girl having a familial MEN1 mutation. She complained of dizziness, occasional palpitation, weakness, hunger, sweating, and generalized tonic-clonic seizure that lasted for 5 minutes early in the morning. At first, she was only diagnosed with insulinoma by abdominal magnetic resonance images of a 1.3 x 1.5 cm mass in the pancreas and high insulin levels in blood of the hepatic vein, but after her father was diagnosed with MEN1. We found she had familial MEN1 mutation, and she recovered hyperinsulinemic hypoglycemia after enucleation of the mass. Therefore, the early genetic identification of MEN1 mutation is considerable for children with at least one manifestation.

PurposeWe studied the changes in subtypes of diabetes mellitus (DM) in children and evaluated the characteristics of each group over the past 20 years. In addition, we also examined the correlation between the glycated hemoglobin (HbA1c) values at the time of diagnosis and lipid profiles.MethodsThe patients were divided into 2 groups: there were a total of 190 patients under 20 years of age firstly diagnosed with DM in Ajou University Hospital. The patients in groups I and II were diagnosed from September 1995 to December 2004 and from January 2005 to April 2014, respectively.ResultsThe characteristics were compared between the 2 groups of patients. The result showed an increase in percentage of type 2 diabetes and maturity onset diabetes of the young (MODY) patients between the 2 groups. HbA1c and total cholesterol level had statistical significances to explain increasing the low-density lipoprotein cholesterol level among age, HbA1c, total cholesterol level, and z-scores of weight and body mass index (BMI) in type 2 diabetes. R-square was 0.074. However, z-score of BMI and total cholesterol level, not HbA1c, had statistical significances in type 1 diabetic patients. R-square was 0.323.ConclusionThe increase in the proportions of both type 2 diabetes and MODY in the last 10 years needed to be reminded when diagnosing the subtypes of DM, and the dyslipidemia should be attended more as a common problem of pediatric diabetic patients.

GH treatment was effective in both children with ISS and those with GHD. Early intervention with GH is the most appropriate therapeutic option in both ISS and GHD.