A Case of Partial Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency Presenting as Uric Acid Lithiasis / 소아과

The deficiency of enzyme hypoxanthine-guanine phosphoribosyltransferase(HPRT) results in hyperuricemia and subsequently manifests in diverse symptoms. Lesch-Nyhan syndrome is a disorder characterized by hyperuricemia, mental retardation, choreoathetosis, spasticity and self-mutilation, resulting from complete deficiency of the enzyme, whereas partial deficiency of the enzyme shows symptoms of milder forms more often without abnormal neurologic signs. A 7-year-old boy with normal growth and psychomotor development presented with a uric acid stone accompanied by a disproportionate increase of serum/urine uric acid level. The stone was removed by nephrolithotomy and further enzymatic study on lysed erythrocytes showed less than 1% of the normal HPRT activity. After initiation of treatment with allopurinol, the uric acid level was rapidly decreased to a normal range and the patient has not shown hyperuricemia or nephropathy since. Although partial HPRT deficiency is not commonly seen, this possibility should be considered whenever urolithiasis is accompanied by disproportionately high levels of serum uric acid.

A Multivariate Analysis of Risk Factors of Renal Involvement in Henoch-Schonlein Purpura / 소아과

PURPOSE: Long-term prognosis of Henoch-Schonlein purpura(HSP) is determined by the existence and severity of renal involvement. We evaluated the relationship between various clinical features of HSP and the development of renal involvement using univariate and multivariate analyses for early detection and proper management of HSP nephritis. METHODS: We performed a retrospective study of 200 children who were diagnosed as HSP and were initially free from renal involvement, from 1998-2003. Clinical features of each patient as risk factors of renal involvement were evaluated by univariate and multivariate analysis. Significant risk factors proven by univariate analysis were paired and re-analyzed to see if there are any interactions between them. RESULTS: A univariate analysis showed that sex, previous disease, severe abdominal symptoms, persistent purpura and steroid administration were associated with developing renal involvement. Among them, severe abdominal symptoms, persistent purpura, and male sex were statistically significant when they were re-analyzed after pairing, and they also increased the risk of renal involvement in a multivariate analysis. CONCLUSION: Severe abdominal symptoms, persistent purpura, and male sex are independent risk factors of renal involvement in HSP and it is presumed that interaction between them could be another factor of HSP nephritis.

Phenotypic Transformation of Tubular Epithelial Cells and Fibroblasts Following Unilateral Ureteral Obstruction or Angiotensin II Infusion in the S-D Rat / 소아과

PURPOSE: Unilateral ureteral obstruction(UUO), a well established experimental model of renal injury, gives rise to tubulointerstitial fibrosis, tubular dilatation and cellular atrophy. Angiotensin(ANG) II may take the prime role in the regulation of this response. The objectives in the current investigation were to determine whether the renal response to UUO involves the dedifferentiation of tubular epithelial cells to mesenchymal cells(expressing vimentin, V) whether the response implicates the transformation of fibroblasts to myofibroblasts(expressing alpha-smooth muscle actin, SMA), and whether these responses depend on the action of ANG II or not. METHODS: Unilateral ureteral ligation and sham operations were performed in 12 adult male Sprague-Dawley rats. An additional 18 rats received exogenous ANG II at 50 ng/min or vehicle for one week using an osmotic minipump inserted into the interscapular area. Rats were sacrificed on postoperative day seven or day 14. To know the expression of vimentin(V) and alpha-smooth muscle actin (SMA) proteins, immunohistochemical staining and Western blot assay were done. RESULTS: In immunohistochemical staining, following UUO, V-positive cells appeared markedly in the interstitium and tubular cells within dilated tubules. UUO also markedly increased alpha-SMA expression in the interstitium surrounding dilated tubules. In Western blotting, UUO increased V(five times of Sham) and alpha-SMA(2.5 times of Sham) expression. ANG II infusion increased alpha-SMA significantly(two times of control), but not V expression in Western blotting. CONCLUSION: Phenotypic transformation of fibroblasts to myofibroblasts following UUO may depend on ANG II, but dedifferentiation of tubular epithelial cells may depend on other mechanisms rather than ANG II.

Effects of Ascorbic Acid on Keratinocyte and Epidermalization of Skin

BACKGROUND: There are different models of skin substitutes, but no skin substitutes have the characteristics of native skin. It was reported that the incubation of skin substitutes in medium containing ascorbic acid extends cellular viability and promotes formation of an epidermal barrier in vitro. OBJECTIVE: The purpose of this study is to observe the effects of ascorbic acid on the proliferation of keratinocytes and on the reconstruction of epidermis. MATERIALS AND METHODS: Normal human keratinocytes and fibroblasts were isolated and used for culturing living skin equivalent (LSE). RESULTS: When ascorbic acid was added, the expression of p63 and a6 integrin was definitely increased compared to control models. In addition, ascorbic acid increased the proliferation of normal human keratinocytes at a dose dependent manner. Especially, ascorbic acid induced the phosphorylation of ERK and up-regulation of EGF-R CONCLUSION: Results suggest that ascorbic acid is essential in the control of keratinocyte proliferation and basement membrane formation. Ascorbic acid-related keratinocytes proliferation is seemed to be mediated by ERK phosphorylation and EGF-R up-regulation.

A Case of Schinzel-Giedion Syndrome

Schinzel-Giedion syndrome is a rare, distinct dysmorphic syndrome characterized by congenital hydronephrosis, skeletal dysplasia, and severe developmental retardation, likely to be inherited as an autosomal recessive trait, but not yet confirmed. This syndrome is characterized by coarse facial features such as midfacial retraction, bulging forehead, short nose with anteverted nostrils, low-set malformed ears, protruding large tongue, and hypertelorism. Skeletal and limb defects, choanal stenosis, simian creases, hypospadias, microphallus, hypertrichosis, and intractable seizures are the frequently associated clinical findings. Urogenital involvement is a major component of the syndrome, and this problem sometimes is associated with nephrocalcinosis and urinary tract infection in the clinical course of the disease. We report a 22 month-old girl with Schinzel-Giedion syndrome complicated by medullary nephrocalcinosis and urinary tract infection due to Klebsiella pneumoniae. This patient had also been suffering from postnatal growth deficiency, intractable seizure, spastic tetraplegia, delayed development and severe mental retardation.

Alport Syndrome Associated with Poststreptococcal Glomerulonephritis in Brothers

Alport syndrome is the most common type of hereditary nephritis, and acute poststreptococcal glomerulonephritis(APSGN) is a common disease in children. We experienced the clinical and pathologic findings of Alport syndrome and APSGN in brothers of one family. Both patients presented with heavy gross hematuria and proteinuria. ASO titer was elevated in both cases, and the C3 level was reduced in one of the cases. In renal pathology, both showed characteristics of Alport syndrome as well as the glomerular changes of APSGN with hump-like subepithelial deposits by electron microscopy. These clinical observation indicated that the patients had APSGN superimposed on Alport syndrome, and that the episode of APSGN might exacerbate the clinical course of Alport syndrome.

Childhood Acute Immune Thrombocytopenic Purpura in Korea: Multicenter Study of Korean Society of Pediatric Hematology/Oncology / 대한소아혈액종양학회지

PURPOSE: Childhood acute immune thrombocytopenic purpura (ITP) is a benign hematologic disease. Therapy does not affect the natural history of the illness. We evaluated the clinical and laboratory findings, treatment and prognosis of childhood acute ITP in Korea through a retrospective multicenter study. METHODS: We analyzed retrospectively the data of 1, 829 children with acute ITP through survey of 33 hospitals among 43 hospitals in Korea from Sep. 1992 to Aug. 2001. RESULTS: Male to female ratio was 1.3: 1 and the median age at the diagnosis of ITP was 2.9 (0.1 17) years. Median duration of follow up was 6 months. One hundred and forty nine cases of the total 1, 829 patients (8.1%) received no treatment. The initial median platelet count of the non-treated group was 42, 500/mm3. Among the 861 cases who were followed up over 6 months, 315 cases (36.6%) progressed into chronic ITP. Associated with this high rate of chronicity of childhood acute ITP patients in Korea, we must consider the fact that acute ITP patients with fast improvement in the first episode tend not to follow up. Considering that fact, the rate of chronicity becomes 17.2% of the 1, 829 acute ITP patients. The treated group used many kinds of treatment methods. Intravenous immunoglobulins (IVIG) with or without prednisolone (PD) (67.5%) were the most commonly used regimens. In the group treated with IVIG alone, the platelet count began to rise above 50, 000/mm3 at 2.6 days, 100, 000/mm3 at 3.7 days and 150, 000/mm3 at 4.9 days. Four hundred and twenty two cases of the 1, 686 (25.0%) cases followed up after first episode of ITP relapsed. The relapse rate was significantly higher in older patients and in girls than in younger patients and in boys (P< 0.05). The chronicity of ITP statistically increased with age (P< 0.05) and that was the only valuable factor. CONCLUSION: Despite the fact that childhood acute ITP is a pretty common disaese, there is no agreement on the best treatment method for this disease. The establishment of Korean treatment guideline of childhood acute ITP, based on an analysis of multicenters, seems to be needed.

Effects of Endothelin A Receptor Antagonist to Cellular Proliferation and Apoptosis in Neonatal Rat Heart

PURPOSE: In order to investigate the role of endothelins in the cardiac development, the present study was designed to examine the effects of endothelin A receptor(ETAR) antagonist to the cellular proliferation and apoptosis in the neonatal rat heart. In addition, the expression of various regulatory genes in protein and mRNA levels by ETAR antagonist were examined. METHODS: Neonatal Spargue-Dawley rats were separated into two groups. The BMS group(N=22) was treated with the selective ETAR antagonist(Bristo-Myers Squibb-182874; 300 mg/Kg/day) and the control group(N=20) with normal saline for seven days by orogastric tube. On the following day, their hearts were harvested for determination of apoptosis by modified TUNEL technique and cellular proliferation by PCNA stain. In addition to this, Western blottings and RT-PCRs of bcl-x, clusterin, p53 and TGF-beta1 were performed. RESULTS: The BMS group resulted in a reduced body weight, but not a significantly reduced heart weight. In the BMS group, cardiac apoptotic cells and PCNA positive cells were decreased(P<0.05). In the BMS group, clusterin and bcl-x protein expressions were increased(P<0.05), but p53 and TGF-beta1 protein expressions remained the same. In the BMS group, clusterin and TGF-beta1 mRNA expressions were increased(P<0.05), but bcl-x and p53 mRNA expressions remained the same. CONCLUSION: ETAR antagonist treatment decreases cell turnover in the developing rat heart, which may account for the role of endothelins on modulating cardiac growth. These changes may be affected by clusterin and bcl-x expressions. These results support that there are some roles of endothelin and ETAR in the cellular level of early neonatal cardiac growth.

Recurrence and Follow-up after Urinary Tract Infection

PURPOSE: Urinary tract infection(UTI) is the most common bacterial infectious disease that may induce severe renal injury unless early diagnosis and appropriate treatment are performed. If recurrent UTI is prevented, renal injury can be also reduced. Therefore, we studied the risk factors of recurrent UTI in children. METHODS: We performed a retrospective study of 168 children(58 girls and 110 boys) who were treated for UTI in the Department of Pediatrics, Korea University Medical Center, during 2000-2001. Among 168 children, 93 children were followed up for more than six months. For the detection of recurrence of UTI, we performed monthly routine urine cultures and physical examinations. RESULTS: The total rate of recurrence was 32.3%. The recurrent rate in boys and girls were 37.1% and 17.4%, respectively(P<0.05). The most common causative bacteria in the first onset and in recurrence were Escherichia coli. There was a significant difference in the onset age of UTI between boys with recurrence(4.8+/-1.0 months) and without recurrence(16.5+/-3.8 months)(P<0.01). In 77% of cases, urinary tract infection recurred within six months of the first infection. The time of the first recurrence after UTI was 3.7+/-0.6 months in boys and 14+/-8.2 months in girls(P<0.01). The number of recurrences showed a significant difference between the group under the age of one year(0.69+/-0.8/year) and those above the age of one year(0.16+/-0.4/year)(P<0.05). There was no difference in the recurrent rate between those with structural abnormality and those with normal anatomy. CONCLUSION: Monthly routine urine cultures are efficient in detecting recurrent UTI in children. Because the male sex and young age especially less than one year of age are risk factors for increased recurrence rate of UTI, these children should be followed-up with urine cultures.

Risk Factors for the First-Year Relapse in Children with Nephrotic Syndrome

PURPOSE: This study aimed to evaluate risk factors of the first year relapse in children with nephrotic syndrome(NS) without the need for biopsy. METHODS: We reviewed, retrospectively, 78 children diagnosed with steroid responsive nephrotic syndrome between July 1997 and June 2002. Median years to follow up were 4.4 years(range: 1-5 years). We divided the patients into two groups(group I: primary responders with no relapse or with only two relapses in the first year after initial response; group II: initial steroid responders with three or more relapses within the first year). We retrospectively reviewed and compared variables - sex, onset age, serum albumin, serum cholesterol, 24 hours urinary protein, creatinine clearance(Ccr), presence of hematuria and hypertension(HTN), and days from initial attack to remission. RESULTS: Of 78 patients(male: 61(78.2%), female: 17(21.8%), age range 1.1 years to 14 years, median 5.1+/-3.0 years), 47(60.3%) were in group I and 31(39.7%) were in group II. There were no statistically significant differences in sex, serum albumin, serum cholesterol, 24 hours urinary protein, Ccr, presence of hematuria or HTN. The median age of onset showed no statistical difference between the two groups. However, if the patients are dividing into two groups according to the age of onset of three-years, patients theree yrs old or less fit into group II, as opposed to patients older than three yrs in age(63.2% vs. 32.2%, P<0.05). The days from initial attack to remission was longer in group II(12.9+/-0.5 vs. 16.2+/-1.1, P<0.05). CONCLUSION: We may conclude that the age of onset of three yrs old or less, and the longer time remission to initial steroid therapy, are risk factors of the first year relapse.

A Case of Intestinal Lymphangiectasia

Intestinal lymphangiectasia, one of the protein-losing gastroenteropathies, is an uncommon disease characterized by dilated intestinal lymphatics, enteric protein loss, edema, hypoalbuminemia, and lympocytopenia. Small bowel biopsy and CT have been used to confirm the diagnosis of intestinal lymphangiectasia. Small bowel biopsy shows collections of abnormal dilated lacteals in submucosa with distortion of villi and CT findings have been described as diffuse nodular thickening of the small bowel and as linear hypodense streaking densities in the small bowel caused by dilated lymphatic channels. Demonstration of increased enteric protein loss using 51Cr-, 131I- or 99mTc-labeled albumin, timed measurement of fecal excretion of radioactivity or by measuring fecal clearance of alpha 1-antitrypsin can also help the diagnosis. We experienced a rare case of intestinal lymphangiectasia in an eight year old boy who presented with facial edema, abdominal distension and intermittent diarrhea. We report a patient with intestinal lymphangiectasia, in whom abdominal CT, 99mTc-labeled albumin scintitigraphy, and stool alpha 1-antitrypsin measurement played key roles in determining the diagnosis. A brief review of literature was made.

Risk Factors for Periventricular Echodensities and Neurologic Outcome in Preterm Infants

PURPOSE: In preterm infants with brain injury, periventricular echodensity is increased transiently or becomes cyst with neurologic sequelae. This study was done to identify the infants who need early rehabilitation treatment by evaluating the risk factors and neurologic outcome in cystic change group and transient echodensity group. METHODS: Thirty one preterm infants with periventricular echodensity on cranial ultrasonography were divided into cystic change group and transient echodensity group. The prenatal, natal, postnatal risk factors and neurologic outcome were evaluated in each group. RESULTS: The risk factors for periventricular cystic change included gestational age, ventilator use, oxygen administration, surfactant use and anemia. The risk factors for transient periventricular echodensity were the same as the cystic change group except gestational age. The development of cerebral palsy occurred in 3 cases out of 10 cases, 2 cases out of 21 cases in each group. CONCLUSION: The preterm infants with periventricular cysts or transient periventricular echodensity need to be observed closely for the development of adverse neurological outcomes especially of those with aforementioned risk factors.

Risk Factors for Periventricular Echodensities and Neurologic Outcome in Preterm Infants

PURPOSE: In preterm infants with brain injury, periventricular echodensity is increased transiently or becomes cyst with neurologic sequelae. This study was done to identify the infants who need early rehabilitation treatment by evaluating the risk factors and neurologic outcome in cystic change group and transient echodensity group. METHODS: Thirty one preterm infants with periventricular echodensity on cranial ultrasonography were divided into cystic change group and transient echodensity group. The prenatal, natal, postnatal risk factors and neurologic outcome were evaluated in each group. RESULTS: The risk factors for periventricular cystic change included gestational age, ventilator use, oxygen administration, surfactant use and anemia. The risk factors for transient periventricular echodensity were the same as the cystic change group except gestational age. The development of cerebral palsy occurred in 3 cases out of 10 cases, 2 cases out of 21 cases in each group. CONCLUSION: The preterm infants with periventricular cysts or transient periventricular echodensity need to be observed closely for the development of adverse neurological outcomes especially of those with aforementioned risk factors.

A Case of Joubert Syndrome Associated with Nephrocalcinosis and Agenesis of Cerebellar Vermis

There are several diseases characterized by neurologic abnormalities and renal disease. Joubert syndrome is one of them. Joubert syndrome is a relatively rare autosomal recessive syndrome. The most significant and constant neurologic finding is hypoplasia of the cerebellar vermis. Joubert syndrome is associated with hypotonia, retinal dystrophy, abnormal eye movement, delayed development, abnormal respiratory pattern (neonatal episodic tachypnea or apnea) and nephronophthisis. We report a boy with Joubert syndrome associated with nephrocalcinosis and agenesis of the cerebellar vermis. This patient had also abnormal eye movement, hypotonia, abnormal respiratory pattern, delayed development and chronic renal failure.

Epidemiology and Clinical Characteristics of Childhood Acute Lymphoblastic Leukemia in Korea / 대한소아혈액종양학회지

PURPOSE: Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of all cases of childhood leukemia. We investigated epidemiology, clinical and laboratory features and treatment outcome of the children with ALL in Korea during recent 5 years. METHODS: One thousand forty nine patients were enrolled between January 1994 and December 1998 from 37 major hospitals in Korea. The data regarding the clinical and laboratory features including age, WBC counts at diagnosis, immunophenotype, morphology, cytogenetics and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed. The differences between groups analyzed by log-rank test. RESULTS: There were 597 males and 452 females. The distribution between the age 2 and 5 years is most common in 46.1%. The annual incidence rate per 100,000 population varied from 1.6 to 2.2. The 5 year event free survival (EFS) rates according to good prognostic factors were as follows: 67% bet ween 1-9 year of age at diagnosis, 69% in under 10,000/mm3of initial WBC count, 74% in early pre-B cell CALLA ( ) immunophenotype, 65% in L3 morphology, 68% in no CNS invasion. Most of patients were treated by CCG treatment protocol. The 5 year EFS was 63%. Main complications were sepsis (21.8%) and hemorrhage (12.5%). The relapse rate was 15.6%. The common causes of death were sepsis, DIC, pneumonia, relapse. CONCLUSION: Our results could provide the most recent and important information about acute lymphoblastic leukemia of children in Korea.

A Family Screening of Patients with Vesicoureteral Reflux

PURPOSE : Vesicoureteral reflux is the most commonly inherited disease detected in children with urinary tract infection. The incidence of vesicoureteral reflux among siblings of children with known vesicoureteral reflux is 8% to 45% according to different authors. Family screening of a patient with vesicoureteral reflux is important in order to prevent reflux nephropathy. The purpose of this study is to determine the incidence of vesicoureteral reflux in asymptomatic family of children with vesicoureteral reflux and the factors which influence the family history. METHODS : The study group consisted of 27 families of patients with vesicoureteral reflux. The total number in the group were 79 persons. BUN, Cr, urineanalysis, voidingcystourethrography(VCUG) and 99mTc -dimercaptosuccinic acid(DMSA) renal scan were performed on the siblings. As for the parents the same tests were performed except the VCUG. RESULTS : The abnormality was detected in 7 of 27 families(25.9%). Vesicoureteral reflux was detected in 5 of 20 siblings and renal scar was detected in 3 of 32 parents. In children with vesicoureteral reflux, renal scar was detected in 24 of 32 children. Between the group with the abnormality in its family(Group A) and the group without the abnormality in its family(Group B), There was no difference of creatinine clearance between two groups. More renal scars were detected in group A according to the DMSA(A:100%, B:75%, t-test p<0.05). There was no difference of grade of VCUG between two groups. There was no difference between one site and both sites in two groups. In the case of the siblings with vesicoureteral reflux, there was high incidence of renal scar in a patient with vesicoureteral reflux according to the DMSA. CONCLUSION : It is important to screen vesicoureteral reflux and renal scar in case of urinary tract infection to prevent reflux nephropathy. This study implies that it is necessary to screen the family of a patient with vesicoureteral reflux especially with renal scar.

Evoked Potentials and Cranial Ultrasonography as a Prognostic Method in Newborn with Asphyxia

PURPOSE: This study was aimed at finding a diagnostic tool which is useful in predicting the neurologic outcome of the asphyxiated newborns. METHODS: 31 newborns with asphyxia were evaluated by brainstem evoked potentials and cranial ultrasonography(CUS). During the neonatal follow-up, we evaluated the development of the babies with Bayley Scale of Infant Development II and INFANIB on corrected age of 14 months. RESULTS: The positive prognostic value of cranial ultrasonography was 72.5% and the negative predictive value was 75.0%. Auditory evoked potential(AEP) showed poor prognostic accuracy in comparison to visual evoked potential(VEP) which showed best prognostic value(85.7%) and somatosensory evoked potential(SEP) with best negative prognostic value(81.3%). CONCLUSION: We would like to emphasize that combined modalities such as SEP snd CUS were more accurate in predicting neurologic outcomes of asphyxiated newborns than evoked potential or CUS read independently. SEP and CUS combination was useful in predicting neurologic outcome of asphyxiated newborn as well as VEP and SEP.

Comparison among Diagnostic Methods of Rotaviral Gastroenteritis in Children / 대한소아소화기영양학회지

PURPOSE: The purpose of this study was to evaluate the clinical efficacy of reverse transcription- polymerase chain reaction (RT-PCR) in detecting rotaviral gastroenteritis in children comparing with that of commercial immunoassays. METHODS: Stools from 79 children admitted Korea University Hospital due to diarrhea were collected from December 1999 to February 2000. Immunoassays were done using commercial rotavirus Latex kit and Rotatec (ELISA) kit. RT-PCR was performed to amplify group A rotavirus, most commonly pathogenic to human, using VP4- and VP7-specific primers. The detection rates of immunoassays and RT-PCR were compared. RESULTS: ELISA assay was superior to LA assay and moderately concordant with RT-PCR in detecting rotaviral gastroenteritis. CONCLUSION: Although RT-PCR is known very sensitive, it does not have significant advantage over immunoassay in detecting rotaviral gastroenteritis.

A Case of Neonatal Lupus Erythematosus with Pancytopenia and Bradycardia

Neonatal lupus erythematosus is a syndrome characterized by congenital heart block and photo-distributed papulosquamous eruption, in which multi-organ involvement is not common. We report a case of neonatal lupus erythematosus with pancytopenia and transient bradycardia. The neonate was born to a mother with systemic lupus erythematosus. Both of the neonate and the mother were positive for anti Ro/SS-A antibody.

A Case of Graves Disease with Kyphosis by Osteoporosis

Graves disease is the most common clinical feature of hyperthyroidism in childhood. Clinical manifestations include emotional lability, hyperactivity, tremor, excessive sweating, exophthalmos and weight loss. In Graves disease, osteoporosis could occur because of a disturbance of mineral homeostasis which rarely develops from reduced calcium absorption of the gastrointestinal tract and increased urinary calcium excretion related to an increased bone resorption. We report a case of Graves disease with spinal deformity caused by osteoporosis in a 12-year-old female who was presented with back pain, anterior neck mass and kyphosis. Laboratory findings revealed hyperthyroidsm, hypercalciuria in 24-hour urine and normal serum parathyroid hormone. On radiologic examination, multiple osteoporosis and a spinal compression fracture were observed. The bone mineral density was decreased at the hip and lumbar spine on the bone densitometry. After initiating antithyroid drug, calcitonin and vitamin D, she returned to a euthyroid state and her back pain was improved. Bone density was also increased one year later.