Identification of a Novel Nonsense Mutation in the ARSE Gene of a Patient with X-Linked Recessive Chondrodysplasia Punctata

X-linked recessive chondrodysplasia punctata (CDPX1) is caused by a hemizygous mutation in the arylsulfatase E (ARSE) gene located on chromosome Xp22.3. It is a rare congenital disorder of punctate calcifications in cartilages, leading to short stature and facial and limb anomalies. These clinical features are frequently observed in all types of chondrodysplasia punctata and have also been seen in other cartilage developmental disorders. Because of the phenotypical similarities, specific testing for only one gene is inefficient and time consuming. The advent of next-generation sequencing has provided an opportunity to improve diagnostic accuracy as well as save on time and cost. Here, we report on a patient diagnosed with CDPX1, who was identified via diagnostic exome sequencing to have a novel nonsense mutation in the ARSE gene, that was inherited from the mother.

Discussion Meeting

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Discussion Meeting

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Stress Responses of Neonates Related to Maternal Characteristics

PURPOSE: To investigate the pre- and post-heelstick stress response patterns of infants and to identify related maternal factors. MATERIALS AND METHODS: Fifty-two mothers and their 57 infants were studied. Stress response patterns in neonates were collected by measurements of pulse rate, oxygen saturation, and salivary cortisol. Maternal demographic factors and awakening saliva were collected. RESULTS: Median level of pulse rate of infant increased from 132.1 to 140.4 beats per minute and salivary cortisol was elevated from 0.41 microg/dL to 0.70 microg/dL during the periods of discomfort, while oxygen saturation decreased from 97% to 95%. Infant's pulse rate change was negatively correlated with gestational age (GA) (r = - 0.37, p < 0.05), whereas the change of infants' salivary cortisol was correlated positively with maternal age (r = 0.29, p < 0.05). GA was the only independently significant predictor of pulse rate responses (R2 = 0.15, p < 0.05). Influence of maternal age on infants' salivary cortisol changes (R2 = 0.09, p < 0.05) was observed in a stepwise multiple regression. CONCLUSION: These findings suggest that maternal age and gestational period can be influential factors for stress responses in infants. Therefore, it would be important to consider the demographic characteristics of mother-infant pairs to evaluate these influential factors.

Bacteremia Detected by a Peripheral Blood Smear in a Pediatric Surgical Patient with Thrombocytopenia / 대한임상미생물학회지

Microscopic examination of peripheral blood smear (PBS) for detection of microorganisms is simple method that can be used for doctors to confirm the septicemia more swiftly and to select more specific therapy. But it is unusual to find microorganisms in PBS. We report a case of gram negative bacteremia diagnosed by PBS in a severe thrombocytopenic pediatric surgical patient. A 6-month and 2 week old baby with cyanosis was diagnosed congenital heart diseases such as transposition of great arteries, atrial septal defect, and patent ductus arteriosus. The infant underwent surgical operations and the postoperative platelet count progressively decreased in spite of transfusion of multiple platelet concentrates. We performed routine examination of a PBS for evaluation of severe thrombocytopenia. The PBS revealed severe thrombocytopenia, leukopenia with left shifted and some extracellular bacilli. Toxic granulations, toxic vacuoles and some bacilli were observed in the neutrophils. The bacilli were identified as Pseudomonas aeruginosa and Serratia marcescens in blood culture. To our knowledge, this is the second case of bacteremia diagnosed by PBS before the positive blood culture in Korea. We suggest that a PBS is useful for the rapid detection of organisms in cases of septicemia with severe thrombocytopenic pediatric surgical patient.

The effect of sucrose on infants during a painful procedure / 소아과

PURPOSE: The purpose of this study was to test the efficacy of treating the pain among newborn infants associated with a medical procedure with sucrose with regard to overall physiological and behavioral stability. METHODS: 103 newborn infants were enrolled in this study. The control group (n=63) did not receive any treatment. The experimental group (n=40) received 2 mL of 24% sucrose solution two minutes before a routine heel stick. The pain was assessed by measurements of physiological changes [e.g. pulse rate, oxygen saturation, salivary cortisol (hydrocortisone)] and behavioral changes [e.g. crying time, and the neonatal infant pain scale (NIPS) for neonates]. RESULTS: There were no differences among the groups with respect to physiological changes associated with the pain from the procedure. However, there were significant group differences in behavioral changes to the pain. In the control group, the median crying time was 13 seconds, while in the experimental group, the median crying time was 3.5 seconds (P=.000). In the control group the median NIPS score was 4, while in the experimental group the median NIPS score was 2 (P=.000). CONCLUSIONS: These findings suggest that sucrose can be an effective method for the management of stress responses in infants with regard to behavior. However, this treatment had no significant physiological effects.

Joubert syndrome with peripheral dysostosis: A case report of long term follow-up / 소아과

This report describes the long-term follow-up of a 10-year-old female patient with Joubert syndrome with short stature and brachydactyly. She presented with hyperpnea alternated with hypopnea, uncontrolled jerking eye movements, and hypotonia during early infancy. She was diagnosed with Joubert syndrome based on clinical symptoms and typical MRI findings at 5 months of age. Abnormal ventilation and eye movements disappeared at around 4 years of age. Head circumference kept within normal range for her age, but her height and weight growth were markedly retarded. Simple X-ray showed an enlarged skull with increased digital markings, hypoplasia of facial bones, and abnormal enchondral bone formations in hands and feet. This article is the first report of Joubert syndrome with peripheral dysostosis.

Effect of Non-Nutritive Sucking on the Oxygen Saturation Level and Behavioral State of Preterm Infants during Tube Feeding

PURPOSE: The main purpose of this study was to evaluate effects of non-nutritive sucking (NNS) on the oxygen saturation level and behavioral state of preterm infants during tube feeding. METHODS: This study was performed prospectively in the NICU, Chonbuk National University Hopspital from November, 2004 through April, 2005. Preterm infants of gestational age 28 to 37 weeks, who had neither major congenital defects interfering feeding nor respiratory difficulty needing ventilatory support, were included. A total of 64 subjects were divided randomly into the control group (n=32), and the non-nutritive sucking (NNS) group (n=32). The patients in each group were tested for changes in oxygen saturation and behavioral state at 3 different times; 2 minutes before, during, and 2 minutes after feeding. RESULTS: The oxygen saturation of the NNS group increased during feeding and gradually decreased after feeding while the control group decreased during feeding and increased slightly after feeding (P<0.001). During feeding, the "quiet awake" state was observed more frequently in the NNS group and the "crying" state was observed more frequently in the control group. During the post-feeding assessment, the "sleep" state was more frequent in the NNS group and the "crying" state was more frequent in the control group. CONCLUSION: The infants in the NNS group showed significantly higher oxygen saturation level and they were less fussy during tube feeding and slept better after feeding.

Comparision of PCR-RFLP, PCR-SSCP, Amplication Refractory Mutation System (ARMS) in Leu72Met Polymorphism of Ghrelin Gene / 소아과

PURPOSE: The role of ghrelin, which promotes the secretion of growth hormone, was not well known until now. Recently it was found that the mutation of ghrelin gene is related to obesity and diabetes. This study is to find the screening method that can easily and effectively detect the polymorphism of Leu72Met in ghrelin gene of obesity patients and apply it to clinical usage. METHODS: We compared PCR-RFLP, PCR-SSCP and ARMS methodologies for analyzing of the polymorphism of Leu72Met in ghrelin gene of obesity children, and also studied the merits and demerits of these methodologies. RESULTS: In this study, we were able to find out the band of peculiar allele of Leu72Met in ghrelin gene using PCR-RFLP, PCR-SSCP and ARMS analyses. The polymorphism of Leu72Met in ghrelin gene determined by all above methodologies was in complete agreement. Compared to the PCR- RFLP and PCR-SSCP, ARMS analysis is simple, inexpensive and also consume less time. It is very sensitive to analyze the polymorphism and easy to understand the results of test. CONCLUSION: Though PCR-RFLP, PCR-SSCP and ARMS analyses were sensitive to analyze the polymorphism of Leu72Met in ghrelin gene, ARMS analysis appears to be more efficient than PCR-RFLP and PCR-SSCP. Therefore, we conclude that ARMS analysis is suitable to analyze the polymorphism of Leu72Met in ghrelin gene for large quantity of specimens.

Novel Gap Junction Molecules, Connexin 37, Enhances the Bystander Effect in HSVtk/GCV Gene Therapy

PURPOSE: Gap junction intercellular communication(GJIC) is an important mechanism of the bystander effect in herpes simplex thymidine kinase/ganciclovir(HSVtk/GCV) gene therapy Therefore, we attempted to enhance the bystander effect in vitro by exogenous overexpressing connexin 37(Cx37) in cells to increase GJIC. METHODS: NIH3T3 cells were transfected with the Cx37 and HSVtk gene or the HSVtk gene alone by the calcium phosphate method, and we detected their expression from these cells by RT-PCR. GCV-mediated cytotoxicity and the bystander effect of each transfectant was then assessed and compared. RESULTS: Cells transfected with HSVtk became sensitive to low concentration of GCV. We found significantly increased cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx37 genes together compared with the cytotoxicity seen after introduction of the HSVtk gene in vitro. Co-expression of the HSVtk and Cx37 genes potentiates HSVtk/GCV gene therapy through the bystander effect. CONCLUSION: These results indicated that the increase of GJIC using Cx37 have potentiated the by stander effect of HSVtk/GCV therapy, and may be a new approach to improve response in suicidal cancer gene therapy.

Alteration of Growth Factor Expression after Acute Ischemic Renal Injury

PURPOSE: Regeneration and repair after ischemic renal injury appears to be modulated by circulating or locally produced growth factors. This study examined the changes of serum insulin like growth factor(IGF-I) and renal expression of IGF-I and II, vascular endothelial growth factor(VEGF), transforming growth factor-beta(TGF-beta), and connective tissue growth factor(CTGF) during the active regeneration period after acute ischemic injury. METHODS: Sera and kidney tissue samples(whole kidney, cortex, outer medullae and inner medullae) were obtained before and after one, three, five and seven days of 40 minutes bilateral renal pedicle clamping. Acute renal failure was assessed by measuring the concentration of serum creatinine. Serum IGF-I level was measured by radioimmunoassay. The mRNA expression in kidney was measured by RT-PCR. The distribution of IGF-I and CTGF was detected by immunohistochemistry. RESULTS: Serum IGF-I concentration after one day following acute ischemic renal injury was significantly decreased compared to preischemic value. The mRNA levels of IGF-I, IGF-II, TGF-beta1 and VEGF in whole kidney were temporally decreased on day one of ischemic injury. IGF-I and IGF-II expressions in outer medullae were significantly decreased on day one after ischemic injury. TGF- beta, CTGF and VEGF expressions were markedly decreased in medullae after one day of ischemic injury compared to other kidney sections. IGF-I was markedly decreased in cortical tubules on day one of uremic rat. CTGF was markedly increased on tubule within three days of ischemic injury. CONCLUSION: These findings suggest that IGFs, TGF-beta and CTGF may involve in the pathogenesis or the recovery from acute ischemic renal injury.

A Case of 13q- Syndrome with Arthrogryposis Multiflex Congenita

13q- syndrome is a rare genetic disorder characterized by psychomotor retardation, hypotonia, microcephaly, retinoblastoma, ptosis and coloboma. Facial and congenital heart anomalies are also found and about 60% of males have genital and anorectal malformations. We report a case of 13q- syndrome male infant with many of afore mentioned features including imperforate anus, penoscrotal inversion, dolichocephaly, large low set ears, micrognathia, bifid scrotum with arthrogryposis, diagnosed by chromosomal analysis using synchronized high resolution G-banding technique which revealed of 46, XY, del(13) (q22) in all 20 metaphases. Echocardiogram and kidney sonogram were normal.

Electrocardiographic and Echocardiographic Characterisitics of Wolff-Parkinson-White Syndrome in Preschool Children

PURPOSE: This study was conducted to estabilish the prevalence, clinical features and relationship between ECG findings and echocardiographic findings of Wolff-Parkinsion-White(WPW) syndrome in asymptomatic preschool children. METHODS: An electrocardiographic screening study was performed on 77,824 preschool children in Jeonbuk province from April, 1999 to August, 2001. Patients with WPW syndrome underwent echocardiographic study. RESULTS: Twenty three patients with WPW syndrome were discovered by electrocardiographic screening of preschool children. The prevalence rate was 2.9 per 10,000 preschool children and there was no significant sexual difference. Two patients had a history of symptoms related to tachyarrythmia. According to the ECG classification of Rosenbaum et al., five patients were type A and 18 were type B. Utilizing the criteria of Gallagher et al, right anterior, 12 patients; right anteiror paraseptal, four patients; left anteiror, three patients. Nineteen of 23 patients underwent echocardiographic study. Four of five patients with type A WPW syndrome had abnormal early systolic anterior motion of left ventricular posterior wall. Twelve of 14 patients with type B had abnormal interventricular septal motion characterized by early sytolic posterior motion immediately after inscription of the delta wave. CONCLUSION: The prevalence rate of preschool children in Jeonbuk province was 2.9/10,000. By the classification according to the electrocardiographic findings, the accessory pathway location was dominant right side than left side. In the echocardiographic study, type A WPW syndrome showed abnormal left ventricular posterior wall motion and type B WPW showed abnormal interventricular septal motion.

The Clinical Manifestations and Results of Medical and Surgical Treatment of Epileptic Children with Neuronal Migration Disorders / 대한소아신경학회지

PURPOSE: The objective of this study is to investige the clinical features, natural histories, and results of medical and surgical treatment of NMD in patients who were diagnosed during childhood. METHODS: We performed a retrospective analysis of medical records of 57 patients with NMD who were newly diagnosed by MRI or pathologically in epilepsy children since March 1993 to June 2000. RESULTS: These 57 patients with NMD consisted of 26 with cortical dysplasia, 9 with lissencephaly, 7 with polymicrogyria, 6 with schizencephaly, 4 with hemimegalencephaly, 3 with heterotopias, and 2 with double cortex. Clinically, 94.7% of these patients showed seizures, 33.3% with developmental delay, 21.1% mental retardation, 15.8% cerebral palsy, and 7.0% attention deficit hyperactivity disorder. Their response to antiepileptic drugs was good to 31 patients (75.6%), moderate to 3 (7.3%), and poor to 7 (17.1%). Twelve patients were completely seizure-free after receiving medication for at least 15 months. Seventeen patients tolerated with monotherapy with antiepileptic drugs. Fourteen patients underwent surgical resection. The results of operation were highly correlated with the complete removal of epileptic focus. Six patients who underwent complete resection were seizure-free after operation. On the other hand, Eight patients who had incomplete resection of the epileptic focus showed poor outcome. CONCLUSION: Most of previous reports suggested that NMD is associated with refractory to medical treatments, and early surgical operation has been recommended. Our study demonstrates remarkably good responses of NMD patients with medical treatment only.

Effect of Antiepileptic Drugs on Bone Metabolism and Growth in Epileptic Children

PURPOSE: Long-term administration of anticonvulsants for children with convulsive disorder may cause osteomalacia, depending on dosage, duration, types, and combination of anticonvulsants administered. This study was performed to examine the effect of anticonvulsant drugs on bone mineral density in epileptic children. METHODS: Forty-eight epileptic children aged 3 to 15 years were enrolled in this study. They were treated with antiepileptic drugs such as carbamazepine(group I), valproic acid(group II), or a combination of several drugs(group III) for long periods time from 6 months to 84 months. Bone mineral density was measured using dual energy absorptiometry(Madison, Wisconsin, U.S.) on the lumbar vertebrae during the period of Dec. 1, 1996-Jul. 1, 1997. Calcium, phosphorus, and alkaline phosphatase were also concomitantly measured in the sera of subjects for comparative analysis. Statistical analysis was performed using drugs and duration of therapy through specific z-score. Analysis for bone mineral density of anticonvulsant treated subjects were compared to results with published data. RESULTS: Bone mineral density was significantly decreased only in the carbamazepine-treated group, especially in children who received carbamazepine therapy for more than 18months. Z-scores of the other groups were also slightly decreased though they were not significant. And serum concentration of calcium and phosphorus levels were within normal ranges, but alkaline phosphatase levels were significantly increased(P<0.01). CONCLUSION: Measurement of bone mineral density might be required in epileptic children who received antiepileptic drugs. Administration of vitamin D should also be recommended in epileptic children, especially if they have been treated with antiepileptic drugs for a long time.

Removal of a Displaced Catheter from Upper GI Tract of a Newborn Using a Goose Neck Snare

For the immediate proper respiratory care of a delivered newborn, the face is wiped immediately, and the mouth and nares should be suctioned. A soft rubber syringe or soft rubber catheter is suitable for suctioning. If respirations are infrequent, suction of the mouth and pharynx serves to stimulate breathing. We experienced a case of a foreign body in the distal esophagus and stomach when the proximal catheter from a DeLee trap catheter was accidentally separated during neonatal repiratory care. Removal of foreign bodies with use of a goose neck snare system is a good retrieval procedure because of its excellent torque control, positive grasping capacity, excellent radioopacity, lack of traumatic effect, and availability in different sizes. We removed the displaced catheter successfully with an Amplatz goose neck snare.

A Case of Congenital Rubella Syndrome

We experienced a case of congenital rubella syndrome manifesting patent ductus arteriosus, petechiae, microcephaly, intrauterine growth retardation, and hepatomegaly in one-day-old female newborn infant. Congenital rubella syndrome was confirmed by positive results of anti-rubella IgM in the sera of patient. Anti-rubella IgM was negative in the sera of mother, while anti-rubella IgG was positive.

The Study of Transplacental Transfer of Immunoglobulin G in Premature Infants

PURPOSE: Premature infants have low serum immunoglobulin G (IgG) levels because IgG is transplacentally acquired, primarily after 32-34 weeks of gestational age. We studied the transplacental transfer of serum IgG in preterm infants. METHODS: The IgG levels in the sera were measured by radial immunodiffusion method (Behring nephelometer, Germany). RESULTS: There was a significant difference between IgG concentration and gestational age; the IgG concentration increased from 462.2 +/- 105.5mg/dL at less than 26 weeks of gestation to 1009.0 +/- 242.6mg/dL at 35 and 36 weeks of gestation with increasing gestational age (P<0.01). The linear relation between IgG concentration and birthweight; the IgG concentration in the sera of premature infants were increased from 588.3 +/- 136.4mg/dL at birthweight less than 1250g to 1149.3 +/- 287.8mg/dL at birthweight more than 2251g with increasing birth weight (P<0.05). CONCLUSION: The effects of gestational age and birthweight on the concentration of IgG at birth were highly interdependent and significant. These results suggest that IVIG administration is needed for nearly all premature infants with birthweight less than 1200g and gestational age less than 32 weeks.

Profile of Insulin, Growth Hormone and Insulin-like Growth Factors in Human Cord Blood According to Birth Weight

PURPOSE: Insulin-like growth factors (IGFs) are mitogenic peptides that are essential for fetal and maternal tissue growth during pregnancy. They circulate primarily with serum IGF-binding protein (IGFBP) which regulates the availability of IGFs to their specific target tissue. This study was performed to examine the relationships between birth weight and IGFs, insulin and growth hormone in the sera of cord blood. METHODS: Fetal serum samples were obtained by direct puncture of the umbilical cord and were stored at -20degrees C until assay. Serum IGF-I, insulin and growth hormone were measured by radioimmunoassay. IGF-II and IGFBP-1 were measured by immunoradiometric assay. RESULTS: The values of insulin, growth hormone, and IGFBP-1 in the cord blood did not significantly correlate with birth weight or gestational age. The values of IGF-I significantly correlated with gestational age (P<0.05). The correlation of IGF-I and birth weight was statistically significant (P<0.05). IGF-II in the sera of cord blood did not significantly correlate with birth weight. CONCLUSION: Cord blood IGF-I level strongly correlated with birth weight, which suggests that IGF-I may play an important role in fetal growth.

A Case of Partial DiGeorge Syndrome / 대한소아내분비학회지

DiGeorge syndrome, a developmental defect of the third and fourth pharyngeal pouches, is characterized by aplasia or hypoplasia of the thymus and parathyroid glands and by conotruncal cardiac malformation. This syndrome is usually associated with deletion of long arm in chromosome 22 (22q11-). We experienced a case of partial DiGeorge syndrome in a 2-month-old male who had hospitalized because of recurrent hypocalcemic tetany and tetralogy of Fallot. Immunologic studies revealed the decreased percentage of T lymphocyte and increased percentage of B lymphocyte. Chromosomal study with high resolution banding, showed 46, XY, 22q13 deletion. We report a case of partial Digeorge syndrome with a brief review of literatures.