Genetic Variations of GNRH1, GNRHR and GPR54 Genes in Korean Girls with Central Precocious Puberty / 대한소아내분비학회지

PURPOSE: Central precocious puberty (CPP) is defined as any sign of secondary sexual maturation appears at an age lower than two standard deviations of the mean for the average age. This process is driven by activation of hypothalamic gonadotropin releasing hormone (GnRH) secretion. Many genes expressed in the hypothalamus have been identified to play an important role in the onset and the progression of puberty. In this study, the GNRH1, its receptor (GNRHR), and kisspeptin receptor (GPR54) genes were scanned to investigate sequence alterations and their distribution in Korean girls with CPP. METHODS: One hundred and one Korean girls with CPP were recruited as the case group and 51 normal Korean women as the control group. The DNAs were extracted and amplified by polymerase chain reaction (PCR), and the products were sequenced directly. Statistical analyses were performed, and P values of C in GNRH1, and c.1091T > A in GPR54. However, the other two (c.196C > T in GNRH1 and c.546T > C in GNRHR) were novel. There was no polymorphism that was significantly associated with early onset or rapid progression of puberty. CONCLUSION: Although the size of our study population was relatively small, simple genetic variations in GNRH1, GNRHR, and GPR54 genes are not likely to be a substantial factor directly associated with the onset and progression of puberty.

Genetic Variations of GNRH1, GNRHR and GPR54 Genes in Korean Girls with Central Precocious Puberty / 대한소아내분비학회지

PURPOSE: Central precocious puberty (CPP) is defined as any sign of secondary sexual maturation appears at an age lower than two standard deviations of the mean for the average age. This process is driven by activation of hypothalamic gonadotropin releasing hormone (GnRH) secretion. Many genes expressed in the hypothalamus have been identified to play an important role in the onset and the progression of puberty. In this study, the GNRH1, its receptor (GNRHR), and kisspeptin receptor (GPR54) genes were scanned to investigate sequence alterations and their distribution in Korean girls with CPP. METHODS: One hundred and one Korean girls with CPP were recruited as the case group and 51 normal Korean women as the control group. The DNAs were extracted and amplified by polymerase chain reaction (PCR), and the products were sequenced directly. Statistical analyses were performed, and P values of C in GNRH1, and c.1091T > A in GPR54. However, the other two (c.196C > T in GNRH1 and c.546T > C in GNRHR) were novel. There was no polymorphism that was significantly associated with early onset or rapid progression of puberty. CONCLUSION: Although the size of our study population was relatively small, simple genetic variations in GNRH1, GNRHR, and GPR54 genes are not likely to be a substantial factor directly associated with the onset and progression of puberty.

PROP1 Gene Analysis in Korean Children with Hypopituitarism / 대한소아내분비학회지

PURPOSE:Mutations of the PROP1 (Prophet of PIT1) gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH)/follicle stimulating hormone (FSH), prolactin (PRL) and adrenocorticotropic hormone (ACTH). We studied the PROP1 mutations in Korean children with hypopituitarism. METHODS:Twelve patients with congenital hypopituitarism were recruited from the Ajou University Hospital, Korea. The pituitary phenotype ranged from isolated growth hormone deficiency (IGHD) to CPHD. Clinical data, including endocrine and neuroradiological data were obtained from the medical records, and the DNA was collected and screened for mutations within PROP1 using polymerase chain reaction (PCR). The PCR products were sequenced directly. RESULTS:Nine patients had abnormal pituitary gland and three patients showed normal pituitary gland in magnetic resonance imaging (MRI). Endocrinologically, seven patients had IGHD and five had CPHD. Three of CPHD had GHD and hypogonadotrophic hypogonadism and the other two had GHD, central hypothyroidism, and ACTH deficiency. We identified no mutations in the PROP1 gene. However, three known polymorphisms were identified: The 27T->C (Ala9Ala) and the associated IVS1+3A->G in exon 1 were found in 25% of patient alleles sequenced. The 424G->A (Ala142Thr) in exon 3 change was identified in 4% of those sequenced. CONCLUSION:This study corresponds to the previous reports that PROP1 mutations are rare in sporadic cases of CPHD. The low mutation frequency in Korean patients may be due to ethnic-specificity or other candidate genes causing this disease. It is necessary to study PROP1 gene and the involved genes in more Korean patients.

Vitamin D Deficiency in Breastfed Infants / 대한소아내분비학회지

PURPOSE: Vitamin D deficiency is a public health problem in many countries. There has been a reappearance of rickets from vitamin D deficiency in recent decades as a result of multiple factors. One of the factors is breast feeding. The purpose of this study was to describe the clinical presentation of rickets in breastfed infants. METHODS: Retrospective review of patients presenting to Ajou University hospital between 2003 and 2008 with rickets caused by vitamin D deficiency during breast feeding. RESULTS: Seventeen patients (10 boys and 7 girls) were diagnosed with vitamin D deficiency. There were six in the asymptomatic and eleven in the symptomatic patients. The mean age of the patients was 8.5+/-0.5 months. The mean 25-hydroxycholecalciferol was 3.55+/-1.88 ng/mL. 25-hydroxycholecalciferol levels were below 5 ng/mL in 13 patients. The mean serum alkaline phosphatase was 765.53+/-563.9 IU/L, the mean intact parathyroid hormone was 231.6+/-225.7 pg/mL. All except 3 patients were showed cupping and fraying of metaphysis. CONCLUSION: Breast feeding is associated with increased risk of rickets. We recommend vitamin D supplementation of all breastfed infants to prevent rickets. Supplementation should begin within the first 2 months of life. Also, we hope to initiate further research and debate about guideline of vitamin D supplementation

Clinical and Biochemical Factors Associated with GnRH Stimulation test in the Idiopathic Central Precocious Puberty and Early Puberty Girls / 대한소아내분비학회지

PURPOSE: Gonadotropin releasing hormone (GnRH) stimulation test is the gold standard method for the diagnosis of central precocious puberty. To predict the result of this test, we studied clinical and biochemical factors associated with the test. METHODS: We evaluated 168 girls under 9 years old with the signs of breast budding and more than one year bone age advancement who underwent this test. We defined the result as two criteria. In the first criteria, positive result of the test means peak LH> or =5 IU/L and peak/basal LH> or =2. In the second criteria, positive result means peak LH> or =5 IU/L, peak/basal LH> or =2 and peak LH/FSH> or =1. RESULTS: In the both first and second criteria, 83 and 31 girls had positive results and other 85 and 137 girls had negative results respectively. In both criteria, the patients with positive results turned out to have more advancement in bone age, smaller predicted adult height, smaller paternal height and higher insulin like growth factor-1 (IGF-1) than those of the patients with negative results. Peak LH was positively correlated with bone age advancement (r=0.35, P<0.001) and IGF-1 (r=0.42, P<0.001) and negatively correlated with predicted adult height (r=-0.22, P=0.01). In multiple logistic regression, bone age was significant predictive factor [first criteria, OR 1.43 (95% CI 1.09, 1.87), P=0.01; second criteria, OR 2.46 (95% CI 1.48, 4.08), P=0.01] of the positive results. CONCLUSION: The result of GnRH stimulation test depends on the degree of breast development and advancement in bone age. Also, IGF-1 is the only positively correlated biochemical factor with the test.

The Effect of Gonadotropin Releasing Hormone Agonist and Growth Hormone on Predicted Adult Height in Girls with Precocious Puberty / 대한소아내분비학회지

PURPOSE: Gonadotropin releasing hormone agonist (GnRH agonist) and growth hormone (GH) treatment is widely used in precocious puberty to delay rapid pubertal growth. We studied the effect of these agents on the predicted adult height in girls with precocious puberty. METHODS: 41 girls were selected who had precocious sexual development, with onset from 5 to 8 years of age. They were divided into two groups. Twenty four girls treated only with GnRH agonist were compared with 17 girls treated with GnRH agonist and GH. We analyzed chronologic age (CA), bone age (BA) and predicted adult height (PAH) during and after treatment. RESULTS: Before treatment, there were no differences for CA, BA, body mass index (BMI), PAH and Tanner stage between two groups. After treatment, the PAH [153.7+/-6.85 cm (-1.31+/-1.25 SDS) vs 158.8+/-5.82 cm (-0.30+/-1.24 SDS)] for both age groups were significantly increased. The difference between initial PAH and follow up PAH was significantly increased when the initial PAH was low (P=0.015), and the duration of treatment was long (P=0.009). CONCLUSION: In girls with precocious puberty, GnRH agonist delayed bone maturation and increased PAH. PAH increased more when GnRH agonist and GH treatment was used as opposed to GnRH agonist treatment alone. GH combination therapy should be considered if the initial PAH was very low.

Prognosis of Proteinuria in Children with Aacute Poststreptococcal Glomerulonephritis(APSGN)

PURPOSE: The prognosis of acute poststreptococcal glomerulonephritis(APSGN) has been reported to be favorable. However, several studies have reported that patients with nephrotic range proteinuria in the acute phase or persistent proteinuria may progress to chronic renal failure. To elucidate this further, we analyzed the features of proteinuria and its prognosis in pediatric patients with APSGN. METHODS: A total of 48 children with APSGN admitted to our hospital between Jan. 2000 and Dec. 2004 were included. After discharge from the hospital, patients were regularly followed up every month by clinical evaluations and laboratory tests including routine urinalysis and quantification of proteinuria. RESULTS: Age of the patients ranged from 3 to 15 years(median 5.8 years) at the time of disease onset. Proteinuria was present in 34(70.8%) patients and 5 of them showed heavy proteinuria. Proteinuria normalized within one month in most patients(82.3%) and there was no one with proteinuria after 6 months. Cyclosporine A(5 mg/kg/day in two divided doses) was given to 3 patients with massive proteinuria that lasted longer than 2 months and the result was complete remission within 4 months. CONCLUSIONS: Our data indicated that the prognosis of APSGN during childhood is excellent. Children with severe proteinuria or subnormal renal function in poststreptococcal glomerulonephritis had favorable prognosis without chronic renal failure, and children with crescentic formation also had favorable prognosis. Three patients who continued to have heavy proteinuria for more than 2 months received cyclosporine A and remission of proteinuria was achieved within a couple of months.

Significances of Echocardiography Using Tissue Doppler Imaging for Children in Growth Hormone Therapy

PURPOSE: The purpose of this study is to evaluate the functional changes of the ventricles for 27 children with recombinant human growth hormone (rhGH) therapy in short stature using echocardiography with tissue Doppler imaging. METHODS: The conventional Doppler echocardiography with tissue Doppler imaging were performed in 27 children with rhGH therapy for short stature and 13 healthy children. Peak velocities of systolic (S) and early (E'), late(A') diastolic wave of mitral annulus,septum and tricuspid annulus were obtained from apical 4 chamber view. RESULTS: There was no differences in left ventricle (LV) mass (72.948+/-11.825 m/s2 vs 73.931+/-12.093 m/s2, P=0.08), LV ejection fraction (66.778+/-5.441% vs 70.154+/-6.641%, P=0.095) and LV fractional shortening (36.737+/-4.265% vs 38.085+/-3.419, P=0.327) were observed between patients and controls. There was no significant differences in E and A measured at mitral and tricuspid annulus were observed between pateints and controls. There was no significant differences in S, E' and A' measured using tissue doppler imaging at mitral annulus, septum, and tricuspid annulus were observed between patients and controls CONCLUSION: No significant differences in parameters of cardiac function using tissue doppler imaging with conventional echocardiography were found between patients with rhGH therapy and controls. But, longer follow-up, involving at a larger number of patients, is required to confirm the safety of long-term rhGH treatment.

Clinical Characteristics of Type 1 Diabetes Mellitus at Initial Diagnosis / 대한소아내분비학회지

PURPOSE: The incidence of type 1 diabetes mellitus is increasing worldwide, the complications such as growth impairment, thyroid dysfunction, microvascular disease can be accompanied in type 1 diabetes mellitus. So, it is important to study initial clinical characteristics of type 1 diabetes mellitus for long-term managements of such complications. METHODS: Forty children and adolescents with type 1 diabetes mellitus who had been followed up in the department of pediatrics, Ajou university hospital from December 1997 to June 2006 were enrolled in this study. Sex, Onset Age, onset season, body mass index, family history, serum blood glucose, urine ketone, admission duration, HbA1c, serum and 24 hours urine C-peptide, islet cell antibody, daily insulin dose, insulin like growth factor-I, thyroid function test, lipid profile, bone age of patients were reviewed retrospectively. RESULTS: Forty patients were enrolled:19 boys and 21 girls. The mean age of diagnosis was 9.2+/-3.5 years. There were no seasonal variation in onset time. The body mass index were 15.9+/-2.7 kg/m2. In family history, 1 patient had type 1 and 16 patients (40%) had type 2 diabetes. Blood glucose was 509+/-172 mg/dL. Urine ketone was positive in 77.8% of patients. HbA1c was 12.5+/-2.4%. Serum C-peptide was 0.76+/-0.65 ng/mL and there was statistically significant positive relationship between patient's age and serum C-peptide level (P<0.05). Daily insulin dose was 0.89+/-0.28 unit/kg/day and negatively correlated with serum C-peptide level (P<0.05), but there were no differences in daily insulin dose between prepubertal and pubertal patients. In 82.4% of patients, at least one of 3 antibody (glutamic acid decarboxylase antibody, islet cell antibody, insulin auto antibody) were detected. Serum C-peptide were higher in GAD Ab positive group than in negative group (P<0.05). In 63.6% of patients, Insulin like growth factor-I levels were lower than normal control group. Thyroid dysfunction were found in 7.5% of patients. 48.7% of patients were accompanied with dyslipidemia. In 51.9% of patients, bone age was advanced by at least 6 months. CONCLUSION: For the most part, our results were consistent with previous studies. But some points like, 1) there was no seasonal variation in onset time, 2) serum C-peptide was not low, 3) there were no differences in daily insulin dose between prepubertal and pubertal patients, differed from previous studies.

A Case of Anterior Ischemic Optic Neuropethy

Anterior ischemic optic neuropathy is due to acute ischemia of the anterior part of the optic nerve, whose main source of blood supply is from the posterior ciliary circulation, either by direct branches or through the peripapillary choroid, with minor and differing contributions from other sources. The clinical features are charaterized by sudden visual impairment, optic nerve related visual field defect and optic disc edema. For pathogenetic as well as therapeutic reasons, these patient can be subdivided into two major subgroups: a nonarteritic group, an arteritic group. The authors experienced a case of AION, which occurred in a young male, probably arteritic. So, the literature of the AION was briefly reviewed and the purpose of this review is to increase awareness of this not uncommon condition.