Response to growth hormone according to provocation test results in idiopathic short stature and idiopathic growth hormone deficiency

Purpose@#To investigate growth response in children with either idiopathic short stature (ISS) or growth hormone (GH) deficiency (GHD). @*Methods@#The data of prepubertal GHD or ISS children treated using recombinant human GH were obtained from the LG Growth Study database. GHD children were further divided into partial and complete GHD groups. Growth response and factors predicting growth response after 1 and 2 years of GH treatment were investigated. @*Results@#This study included 692 children (98 with ISS, 443 partial GHD, and 151 complete GHD). After 1 year, changes in height standard deviation score (ΔHt-SDS) were 0.78, 0.83, and 0.96 in ISS, partial GHD, and complete GHD, respectively. Height velocity (HV) was 8.72, 9.04, and 9.52 cm/yr in ISS, partial GHD, and complete GHD, respectively. ΔHt-SDS and HV did not differ among the 3 groups. Higher initial body mass index standard deviation score (BMI-SDS) and midparental height standard deviation score (MPH-SDS) were predictors for better growth response after 1 year in ISS and the partial GHD group, respectively. In the complete GHD group, higher Ht-SDS and BMI-SDS predicted better growth response after 1 year. After 2 years of GH treatment, higher BMI-SDS and MPH-SDS predicted a better growth outcome in the partial GHD group, and higher MPH-SDS was a predictor of good growth response in complete GHD. @*Conclusion@#Clinical characteristics and growth response did not differ among groups. Predictors of growth response differed among the 3 groups, and even in the same group, a higher GH dose would be required when poor response is predicted.

Morning Glory Syndrome associated with Autosomal Dominant Alport Syndrome with a Heterozygous COL4A4 Mutation

Morning glory syndrome (MGS) is a rare congenital optic disc anomaly with a characteristic fundal finding with severe visual impairment. It may occur in association with various systemic manifestations, even though most of the reported cases were isolated. A 6-year-old male visited the nephrology clinic with a history of microscopic hematuria and at the age of 12 years, he was diagnosed thin glomerular basement membrane nephropathy by kidney biopsy. After the following years, the patient had progressive deterioration of visual acuity, and diagnosed as MGS. Whole Exome Sequencing of this patient and his mother revealed heterozygous COL4A4 mutations [c.81_86del (p.Ile29_Leu30del)]. It is more reasonable to consider MGS seen in this patient as a coincidental finding of autosomal dominant Alport syndrome. To our knowledge, this case represents the first case report of autosomal dominant Alport syndrome associated with MGS.

Identification of a heterozygous ACAN mutation in a 15-year-old boy with short stature who presented with advanced bone age: a case report and review of the literature

Longitudinal bone growth is primarily mediated by the growth plate, which is a specialized cartilaginous structure. Aggrecan, encoded by ACAN, is a primary proteoglycan component of the extracellular matrix in both the growth plate and articular cartilage. Aggrecanopathies have emerged as a phenotype of genetic skeletal disease in humans. A heterozygous ACAN mutation causes short stature, premature growth cessation, and accelerated bone age maturation. We report the case of a 15-year-old boy with familial short stature, with height of 149 cm (Korean standard deviation score [SDS] of -3.6) and weight of 50.5 kg (-1.48 SDS). He presented with mild midfacial hypoplasia, frontal bossing, a broad chest, and a short neck. The father's and mother's heights were 150 cm (-4.8 SDS) and 153 cm (-1.69 SDS), respectively. The patient's bone age was 2–3 years more advanced than his chronological age, and no endocrine abnormalities were detected. Wholeexome sequencing followed by Sanger sequencing revealed a heterozygous ACAN mutation, c.512C>T (p.Ala171Val), in both the proband and his father. Short stature is generally associated with a delayed bone age, and this case suggests that ACAN mutations may be the most likely etiology among patients with short stature and an advanced bone age and should warrant early treatment.

An A627V-activating mutation in the thyroid-stimulating hormone receptor gene in familial nonautoimmune hyperthyroidism

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.

Effects of long-term growth hormone therapy in a girl with Floating-Harbor syndrome

Floating-Harbor syndrome is a rare autosomal dominant disorder that presents with short stature, facial dysmorphism, significantly delayed bone age, skeletal abnormalities, speech and language problems, and intellectual disabilities. Although short stature is one of the main clinical manifestations, use of growth hormone therapy in Floating-Harbor syndrome patients has been limited. Only a few reports have investigated the response to growth hormone therapy with regard to final adult height. We report the case of a 7-year-old girl with FloatingHarbor syndrome and a heterozygous mutation, c.7330C > T (p.Arg2444*), in the SRCAP gene. The patient exhibited dysmorphic facial features, severe intellectual disabilities, obsessive-compulsive and aggressive behaviors, and short stature without growth hormone deficiency. Her height standard deviation score improved after 55 months of growth hormone therapy.

Identification of a heterozygous ACAN mutation in a 15-year-old boy with short stature who presented with advanced bone age: a case report and review of the literature

Longitudinal bone growth is primarily mediated by the growth plate, which is a specialized cartilaginous structure. Aggrecan, encoded by ACAN, is a primary proteoglycan component of the extracellular matrix in both the growth plate and articular cartilage. Aggrecanopathies have emerged as a phenotype of genetic skeletal disease in humans. A heterozygous ACAN mutation causes short stature, premature growth cessation, and accelerated bone age maturation. We report the case of a 15-year-old boy with familial short stature, with height of 149 cm (Korean standard deviation score [SDS] of -3.6) and weight of 50.5 kg (-1.48 SDS). He presented with mild midfacial hypoplasia, frontal bossing, a broad chest, and a short neck. The father's and mother's heights were 150 cm (-4.8 SDS) and 153 cm (-1.69 SDS), respectively. The patient's bone age was 2–3 years more advanced than his chronological age, and no endocrine abnormalities were detected. Wholeexome sequencing followed by Sanger sequencing revealed a heterozygous ACAN mutation, c.512C>T (p.Ala171Val), in both the proband and his father. Short stature is generally associated with a delayed bone age, and this case suggests that ACAN mutations may be the most likely etiology among patients with short stature and an advanced bone age and should warrant early treatment.

An A627V-activating mutation in the thyroid-stimulating hormone receptor gene in familial nonautoimmune hyperthyroidism

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.

Changes in the thyroid hormone profiles in children with nephrotic syndrome / 소아과

PURPOSE: We compared thyroid hormone profiles in children with nephrotic syndrome (NS) during the nephrotic phase and after remission. METHODS: This study included 31 pediatric NS patients. The thyroid hormone profiles included serum levels of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and free T4. RESULTS: Of the 31 patients, 16 (51.6%) showed abnormal thyroid hormone profiles: 6 had overt hypothyroidism, 8 had subclinical hypothyroidism, and 2 had low T3 syndrome. The mean serum T3, T4, and free T4 levels in the nephrotic phase and after remission were 82.37±23.64 and 117.88±29.49 ng/dL, 5.47±1.14 and 7.91±1.56 µg/dL, and 1.02±0.26 and 1.38±0.23 ng/dL, respectively; the levels were significantly lower in the NS nephrotic phase (P=0.0007, P<0.0001, and P=0.0002). The mean serum TSH levels during the nephrotic phase and after remission were 8.05±3.53 and 4.08±2.05 µIU/ mL, respectively; they were significantly higher in the nephrotic phase (P=0.0005). The urinary protein/ creatinine ratio during the nephrotic phase was significantly correlated with serum T3, T4, and free T4 levels (r=-0.5995, P=0.0032; r=-0.5797, P=0.0047; r=-0.5513, P=0.0078) as well as with TSH levels (r=0.5022, P=0.0172). A significant correlation was found between serum albumin and serum T3 levels during the nephrotic phase (r=0.5385, P=0.0018) but not between serum albumin and T4, TSH, or free T4 levels. These significant correlations all disappeared after remission. CONCLUSION: Abnormal thyroid hormone profile findings were observed in 51.6% of pediatric patients with NS. Thyroid hormone levels normalized after remission, regardless of levothyroxine therapy.

A Rare Case of Hyponatremia Caused by Reset Osmostat in a Neonate with Cleft Lip, Cleft Palate, and Imperforate Anus

Hyponatremia is defined as a plasma sodium concentration of < 135 mEq/L. It is a common electrolyte imbalance in newborns. We report the case of a term neonate with cleft lip, cleft palate, imperforate anus, normal male karyotype, and chronic hyponatremia. On the 4th day of life, he showed hyponatremia (plasma sodium concentration 130 mEq/L) with low serum osmolality (275 mOsm/kg), high urine sodium (116.7 mEq/L), and high urine osmolality (412 mOsm/kg). His thyroid and adrenal functions were normal. Despite intravenous and oral sodium supplementation and hydrocortisone treatment, hyponatremia persisted. Brain magnetic resonance imaging showed normal results. He was diagnosed as having reset osmostat, a rare subtype of the syndrome of inappropriate secretion of antidiuretic hormone characterized by a subnormal threshold for antidiuretic hormone secretion, with hypotonic hyponatremia.

The influence of gonadotropin releasing hormone agonist treatment on the body weight and body mass index in girls with idiopathic precocious puberty and early puberty

PURPOSE: This study aimed to investigate the influence of gonadotropin releasing hormone agonist (GnRHa) treatment on the weight and body mass index (BMI) of girls who were diagnosed with idiopathic central precocious puberty (CPP) or early puberty (EP). METHODS: Patients who were younger than 8 years of age at diagnosis were classified as CPP and patients aged between 8 and 9 years at diagnosis were classified as EP. Of 129 patients, 34 were diagnosed with CPP and 95 were diagnosed with EP. The patients were divided according to pretreatment weight status into normal weight group, an overweight group, or an obese group. RESULTS: No significant changes were observed with respect to the weight standard deviation score (SDS) before and after 1 year, 2 years of treatment, respectively (P>0.05, P>0.05) in all patient groups. No significant changes were observed in relation to the BMI SDS before and after 1 year, 2 years of treatment, respectively (P>0.05, P>0.05) in all patient group. Depending on the degree of obesity, differences with respect to the weight SDS and BMI SDS were observed. CONCLUSION: BMI SDS increased in the GnRHa-treated patients as a whole group, but was not statistically significant. But BMI SDS increased significantly in the normal weight group after 2 years of GnRHa treatment. So, GnRHa treatment may affect the change of BMI SDS depending on degree of obesity.

A 10-year-old Boy with Microscopic Hematuria and Renal Biopsy Findings Mimicking Fabry Disease

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A, resulting in the accumulation of glycosphingolipids within the lysosomes of various cell types. It has a wide spectrum of clinical phenotypes, and renal failure is a serious complication. Fabry disease is confirmed either by measurement of α-galactosidase A activity or by genetic testing for GLA mutations. Renal biopsy findings on light microscopy, specifically enlarged podocytes with foamy cytoplasm, and osmiophilic inclusion bodies in the cytoplasm in all types of renal cells on electron microscopy, are characteristic of this disease. The predominant differential diagnosis is iatrogenic phospholipidosis in association with certain drugs that can cause cellular injuries indistinguishable from Fabry disease. Here, we report the case of a 10-year-old boy with microscopic hematuria who underwent a renal biopsy that showed morphological findings consistent with Fabry disease, although the patient had neither a GLA mutation nor a history of drug consumption. Six years later, spontaneous regression of this renal pathology was observed in a second renal biopsy examination.

Targeted exome sequencing resolves allelic and the genetic heterogeneity in the genetic diagnosis of nephronophthisis-related ciliopathy

Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end-stage renal failure during childhood and adolescence and exhibits an autosomal recessive pattern of inheritance. Genetic diagnosis is quite limited owing to genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step-wise screening of Sanger sequencing and targeted exome sequencing for the genetic diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by Sanger sequencing in phenotypically classified patients. Known pathogenic mutations were identified in 12 patients (21.8%); homozygous deletions of NPHP1 in 4 juvenile nephronophthisis patients, IQCB1/NPHP5 mutations in 3 Senior–Løken syndrome patients, a CEP290/NPHP6 mutation in 1 Joubert syndrome patient, and TMEM67/MKS3 mutations in 4 Joubert syndrome patients with liver involvement. In the remaining undiagnosed patients, we applied targeted exome sequencing of 34 ciliopathy-related genes to detect known pathogenic mutations in 7 (16.3%) of 43 patients. Another 18 likely damaging heterozygous variants were identified in 13 NPHP-RC genes in 18 patients. In this study, we report a variety of pathogenic and candidate mutations identified in 55 patients with NPHP-RC in Korea using a step-wise application of two genetic tests. These results support the clinical utility of targeted exome sequencing to resolve the issue of allelic and genetic heterogeneity in NPHP-RC.

Incidence trends and associated factors of diabetes mellitus in Korean children and adolescents: a retrospective cohort study in Busan and Gyeongnam

PURPOSE: This study investigated the incidence trends and associated factors of type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in children and adolescents under 15 years of age in Busan and Gyeongnam, Korea from 2001 to 2010. METHODS: Medical records of newly diagnosed diabetes patients (n=328; 160 males, 168 females) were collected in questionnaire form from 5 tertiary and 42 general hospitals in Busan and Gyeongnam. RESULTS: The average crude incidence rate of T1DM and T2DM was 2.01/100,000 (95% confidence interval [CI], 1.76-2.28) and 0.75/100,000 (95% CI, 0.60-0.92), respectively. The incidence rate ratio (IRR) of T1DM was 1.31 (95% CI, 1.01-1.69), and that of T2DM was 1.97 (95% CI, 1.25-3.11) in the latter half-decade (2006 to 2010) compared to the early half-decade (2001 to 2005). There were gradually increasing incidence trends in both T1DM and T2DM over the 10-year period (P for trend: T1DM, 0.0009; T2DM, <0.0001). Age-specific IRR was highest in the 10- to 14-year-old group, regardless of diabetes type. In particular, a rapid increase in incidence of T2DM occurred in the 10- to 14-year-old group. IRR for females was 1.07 (95% CI, 0.83-1.38) for T1DM and 1.56 (95% CI, 1.01-2.41) for T2DM. IRR for Busan (urban) was 1.41 (95% CI, 1.09-1.83) for T1DM and 1.49 (95% CI, 0.96-2.30) for T2DM. CONCLUSION: T1DM and T2DM incidence both increased over time in youth under age 15 living in Busan and Gyeongnam; in particular, the incidence of T2DM in adolescents increased more rapidly.

Renal Problems in Early Adult Patients with Turner Syndrome

PURPOSE: This study aimed to evaluate the status of renal function and the presence of urinary abnormalities in early adult patients with Turner syndrome (TS). METHODS: Sixty-three girls with TS, who are attending pediatric endocrine clinics in Busan Paik Hosp., were studied. Urine and blood chemistry tests were performed in every visiting times. Renal ultrasonography was performed in all patients at the initial diagnosis, and intravenous pyelography, DMSA renal scan and renal CT were also performed, if necessary. RESULTS: Of the 63 patients, the karyotype showed 45,X in 32 (50.8%) , mosaicism in 22 (34.9%) and structural aberration in 9 (14.3%). The renal function at the latest visit was shown as normal in all patients. Nephrotic syndrome had developed in one patient. Hematuria was observed in seven patients. Renal anomalies were observed in 20 of the 63 TS (31.7%). Of the 32 TS patients with 45,X karyotype, 13 (40.6%) had renal anomalies, while these were found in 7 (22.6%) of 31 TS patients with mosaicism/structural aberration. But there was no significant statistical difference between two karyotype groups. CONCLUSION: Based on this study, most of the patients with TS do not have any significant problems related to renal function until early adulthood, regardless of renal malformation or hematuria.

Efficacy of Short-Term Growth Hormone Treatment in Prepubertal Children with Idiopathic Short Stature

PURPOSE: It has been reported that daily recombinant human growth hormone (GH) treatment showed beneficial effects on growth in prepubertal children with idiopathic short stature (ISS). The present study aimed to validate the GH (Eutropin(R)) effect on growth promotion and safety after short-term GH treatment. MATERIALS AND METHODS: This study was an open-label, multicenter, interventional study conducted at nine university hospitals in Korea between 2008 and 2009. Thirty six prepubertal children with ISS were enrolled in this study to receive 6-month GH treatment. Yearly growth rate, height standard deviation score (SDS), and adverse events were investigated during treatment. RESULTS: After 26 weeks of GH treatment, the height velocity significantly increased by 6.36+/-3.36 cm/year (p<0.001). The lower end of one-sided 95% confidence interval was 5.22 cm/year, far greater than the predefined effect size. The gain in height SDS at week 26 was 0.57+/-0.27 (p<0.0001). Bone age significantly increased after GH treatment, however, bone maturation rate (bone age for chronological age) showed limited advancement. This 26-week GH treatment was effective in increasing serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 from baseline (p<0.0001). Eutropin was well tolerated and there were no withdrawals due to adverse events. No clinically significant changes in laboratory values were observed. CONCLUSION: This 6-month daily GH treatment in children with ISS demonstrated increased height velocity, improved height SDS, and increased IGF-I and IGFBP-3 levels with a favorable safety profile.

Insulin autoimmune syndrome induced by methimazole in a Korean girl with Graves' disease

Hypoglycemia was detected in a 15-year-old girl due to loss of consciousness. She was diagnosed with Graves' disease and was being treated with methimazole for the past 4 months. A paradoxically increased insulin levels was found when she suffered from the hypoglycemic episode. An imaging study showed no mass lesion in the pancreas, and insulin antibodies were found in the serum. She was diagnosed with insulin autoimmune syndrome. Her HLA typing was performed, and it revealed HLA-DRB1 *04:06. The patient was treated with a corticosteroid for 2 months. After discontinuing the steroid, the insulin antibody titer decreased dramatically, and she did not have any episode of hypoglycemia since. This is the first report of insulin autoimmune syndrome in a Korean girl, and we have revealed the connection between HLA type and insulin autoimmune syndrome in Korea.

Clinical Manifestations and Characteristics in Patients with Horseshoe Kidney

PURPOSE: We aimed to investigate the clinical characteristics and associated diseases in children with a horseshoe kidney and compared these data between children and adults. METHODS: We performed a retrospective analysis of the medical records and radiological findings of 43 patients diagnosed with a horseshoe kidney in the Busan Paik Hospital. The subjects were divided into the children's group (14 cases, age or =18 years). RESULTS: The study group consisted of 17 males and 26 females with a median age of 34 years. In the children's group (14 cases), 5 subjects were male and 9 were female, with a mean age of 6.7+/-6.2 years. Most of the subjects were asymptomatic and were incidentally diagnosed with horseshoe kidney during their evaluation for another disease. Among the associated diseases in the children's group, Turner syndrome was the most common (5 cases), whereas ureteropelvic junction (UPJ) stricture was observed in 2 cases (14.2%). None of the children exhibited abnormal renal function during the follow-up period. In the adult group (29 cases), 12 subjects were male and 17 were female, with a mean age of 48 years. Eighteen patients were incidentally diagnosed with horseshoe kidney during their evaluation for another disease, and 11 patients had hematuria or abdominal pain due to renal stones. Among the associated diseases in the adult group, Turner syndrome was the most common (5 cases), and UPJ stricture was observed in 5 cases; the other accompanying diseases included hydronephrosis and overactive bladder. Six patients exhibited decreased renal function (serum creatinine level >1.5) during the follow-up period. CONCLUSION: Horseshoe kidney is usually diagnosed incidentally in both children and adults. In the present study, we noted that Turner syndrome was the most common associated disease in children. In addition, most children were asymptomatic but had a high risk of urologic complications after the transition to adulthood. Therefore, children with horseshoe kidney require continuous follow-up.

Evaluation of Cardiovascular Anomalies in Patients with Asymptomatic Turner Syndrome Using Multidetector Computed Tomography

Turner syndrome is well known to be associated with significant cardiovascular abnormalities. This paper studied the incidence of cardiovascular abnormalities in asymptomatic adolescent patients with Turner syndrome using multidetector computed tomography (MDCT) instead of echocardiography. Twenty subjects diagnosed with Turner syndrome who had no cardiac symptoms were included. Blood pressure and electrocardiography (ECG) was checked. Cardiovascular abnormalities were checked by MDCT. According to the ECG results, 11 had a prolonged QTc interval, 5 had a posterior fascicular block, 3 had a ventricular conduction disorder. MDCT revealed vascular abnormalities in 13 patients (65%). Three patients had an aberrant right subclavian artery, 2 had dilatation of left subclavian artery, and others had an aortic root dilatation, aortic diverticulum, and abnormal left vertebral artery. As for venous abnormalities, 3 patients had partial anomalous pulmonary venous return and 2 had a persistent left superior vena cava. This study found cardiovascular abnormalities in 65% of asymptomatic Turner syndrome patients using MDCT. Even though, there are no cardiac symptoms in Turner syndrome patients, a complete evaluation of the heart with echocardiography or MDCT at transition period to adults must be performed.

Mutational Analysis of Mitochondria DNA in Children with IgA Nephropathy

PURPOSE: The association of mitochondrial DNA (mtDNA) mutations, deletions and copy number with progressive changes in patients with some glomerular disease and end-stage renal disease have been reported. In this study, we performed mtDNA mutation analysis in children with IgA nephropathy to investigate its role in progressive clinical course. METHODS: Seven children with IgA nephropathy were involved in this study. MtDNA isolated from platelet was amplified by PCR and sequenced entirely. RESULTS: The mean age at renal biopsy was 11.5+/-2.2 year and the mean age at latest evaluation was 17.9+/-3.2 year. The mean follow-up period were 7.8+/-3.1 years. Patients was divided into 2 groups according to the amount of proteinuria at presenting manifestation. Group 2 patients were nephrotic syndrome. Renal function reveals within normal range in all patients. In group 2 patients, the mean serum albumin level was significantly lower than those of group 1 (3.7+/-0.6 g/dL vs. 4.7+/-0.2 g/dL, P=0.0241) and the mean total cholesterol level was significantly higher than those of group 1 (222.7+/-35.7 mg/dL vs. 148.3+/-29.1 mg/dL, P=0.0283). In Group 2 patients, total amount of protein of 24 hour collected urine also significantly higher than those of group 1 (1,466.0+/-742.5 mg vs. 122.5+/-48.1 mg, P=0.0135). Pr/Cr ratio in random urine sample was also higher in group 2 than those of group 1 but the statistical significance was not noted (1.8+/-1.6 vs. 0.2+/-0.2, P=0.0961). Deletion of mtDNA nt 8272-8281 were observed in two patients, one patient in each groups, respectively. This is non-coding lesion. No patients demonstrated the mtDNA mutations. CONCLUSIONS: We have identified a deletion of mtDNA nt 8272-8281 in two children with IgA nephropathy. Further studies are needed to clarify the role of mitochondrial function in the progressive change of IgA nephropathy.

Medullary Sponge Kidney Detected in the Pediatric Age

PURPOSE: Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilatation of precalyceal collecting tubules. MSK incidence and prevalence in the general population is uncertain and only a few patients are reported especially in the pediatric age. There has been increasing reports of patients with MSK who have other malformative disorders. Also several case reports concerning about etiological association of some genes. METHODS: Collaborative study through nation-wide survey was done to investigate the incidence and etiological association of some genes such as GDNF gene, ATP6V1B1, ATP6V0A4 gene in developing MSK in Korean children. RESULTS: Four cases of MSK who have various other malformative disorders were collected. There are no mutations of GDNF gene, ATP6V1B1, ATP6V0A4 gene in all patients. CONCLUSION: MSK is one of the very rare diseases in pediatric age. The etiological association of GDNF gene , ATP6V1B1, ATP6V0A4 gene in developing MSK in Korean children is not proved.