Autosomal Recessive Malignant Infantile Osteopetrosis Associated with a TCIRG1 Mutation: A Case Report of a Neonate Presenting with Hypocalcemia in South Korea

Osteopetrosis refers to a group of genetic skeletal disorders characterized by osteosclerosis and fragile bones. Osteopetrosis can be classified into autosomal dominant, autosomal recessive, or X-linked forms, which might differ in clinical characteristics and disease severity. Autosomal recessive osteopetrosis, also known as malignant osteopetrosis, has an earlier onset, more serious clinical symptoms, and is usually fatal. We encountered a 1-day-old girl who was born full-term via vaginal delivery, which was complicated by meconium-stained amniotic fluid, cephalo-pelvic disproportion, and nuchal cord. Routine neonatal care was provided, in addition to blood tests and chest radiography to screen for sepsis, as well as skull radiography to rule out head injuries. Initial blood tests revealed hypocalcemia, which persisted on follow-up tests the next day. Radiographic examinations revealed diffusely increased bone density and a "space alien" appearance of the skull. Based on radiographic and laboratory findings, the infantile form of osteopetrosis was suspected and genetic testing for identification of the responsible gene. Eventually, a heterozygous mutation of the T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 (TCIRG1) gene (c.292C>T) was identified, making this the first reported case of neonatal-onset malignant osteopetrosis with TCIRG1 mutation in South Korea. Early-onset hypocalcemia is common and usually results from prematurity, fetal growth restriction, maternal diabetes, perinatal asphyxia, and physiologic hypoparathyroidism. However, if hypocalcemia persists, we recommend considering 'infantile of osteopetrosis' as a rare cause of neonatal hypocalcemia and performing radiographic examinations to establish the diagnosis.

Autosomal Recessive Malignant Infantile Osteopetrosis Associated with a TCIRG1 Mutation: A Case Report of a Neonate Presenting with Hypocalcemia in South Korea

Osteopetrosis refers to a group of genetic skeletal disorders characterized by osteosclerosis and fragile bones. Osteopetrosis can be classified into autosomal dominant, autosomal recessive, or X-linked forms, which might differ in clinical characteristics and disease severity. Autosomal recessive osteopetrosis, also known as malignant osteopetrosis, has an earlier onset, more serious clinical symptoms, and is usually fatal. We encountered a 1-day-old girl who was born full-term via vaginal delivery, which was complicated by meconium-stained amniotic fluid, cephalo-pelvic disproportion, and nuchal cord. Routine neonatal care was provided, in addition to blood tests and chest radiography to screen for sepsis, as well as skull radiography to rule out head injuries. Initial blood tests revealed hypocalcemia, which persisted on follow-up tests the next day. Radiographic examinations revealed diffusely increased bone density and a "space alien" appearance of the skull. Based on radiographic and laboratory findings, the infantile form of osteopetrosis was suspected and genetic testing for identification of the responsible gene. Eventually, a heterozygous mutation of the T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 (TCIRG1) gene (c.292C>T) was identified, making this the first reported case of neonatal-onset malignant osteopetrosis with TCIRG1 mutation in South Korea. Early-onset hypocalcemia is common and usually results from prematurity, fetal growth restriction, maternal diabetes, perinatal asphyxia, and physiologic hypoparathyroidism. However, if hypocalcemia persists, we recommend considering 'infantile of osteopetrosis' as a rare cause of neonatal hypocalcemia and performing radiographic examinations to establish the diagnosis.

Effects of Topical Anesthetics to Reduce Pain in Preterm Infants During Percutaneous Cental Venous Catheterization (PCVC) / 대한주산의학회잡지

PURPOSE: The purpose of this study is to prove the effects of topical anesthetics (EMLA) to control pain in preterm infants during invasive procedure (percutaneous central venous catheterization, PCVC). METHODS: A total of 18 preterm infants of birth weight <2,000 g and gestational age <36 weeks born at EulJi University Hospital, at Daejeon in 2010 were randomly included in this study. EMLA was applied in nine preterm infants 40 minutes before starting PCVC and placebo was applied in another nine preterm infants. Based on PIPP (preterm infant pain profile), we evaluated their heart rate, oxygen saturation before, 15 seconds during and 30 seconds after procedure. Behavioral responses were also recorded for 2 minutes after procedure. RESULTS: Experimental group showed significantly less behavioral response during procedure (P=0.005) and 2 min after procedure (P=0.001). Also, experimental group showed less increase in heart rate (P=0.033) and reduction of behavioral state (P=0.017). CONCLUSION: Despite limitation of small size in this study, experimental group showed lower pain score compared with placebo control group during catheterization. In neonatal care unit (NICU), we recommend the use of topical anesthetics such as EMLA to control pain during invasive procedures.

Risk Factors for Neonatal Infections in Full-term Babies in South Korea

PURPOSE: Since 1997, private postnatal care facilities (San-hu-jo-ri-won in Korean) have emerged to take the role of the family. As a result, neonates are now exposed to many people and are very vulnerable to infection. However, there has been no study on the influence of postnatal care facilities on neonatal infection. The aim of this study was to determine the risk factors of neonatal infection in full-term babies in Korea. MATERIALS and METHODS: We followed up 556 pregnant women and their babies for 4 weeks after their births at 2 hospitals in Seoul and Daejeon from October 2004 to September 2005. Among 512 full-term babies, 58 had infectious diseases. To determine the risk factors for infection, 53 infected neonates at 4-28 days of life and 413 healthy neonates were compared. RESULTS: The incidence of neonatal infection at 4 to 28 days after birth was 10.5%. After adjusting the related factors, the number of siblings (OR = 2.05, 95% CI = 1.13-3.71 for 1 or more) and postnatal care facilities or home aides (OR = 1.91, 95% CI = 1.07-3.45) were significant risk factors. Formula or mixed feeding (OR = 1.66, 95% CI = 0.91-3.04) increased the risk of neonatal infection but it was not statistically significant. CONCLUSION: When the newborns had siblings, stayed at postnatal care facilities, or were cared for by home aides, the risk of neonatal infections significantly increased. Further research on the feeding effect on neonatal infection and evaluation of prevention efforts are needed.

Neonatal Sepsis Caused by Multi-Resistant Streptococcus Mitis

PURPOSE: Streptococcus mitis, one of the Viridans streptococci, is a normal female genital tract flora. It is known as a common cause of chorioamnionitis and subsequent abortions in perinatal period. Although it has been suggested to be less virulent they can cause severe neonatal infections. In this study, we focused on the clinical presentations of neonatal septicemia and the antibiotic susceptibilities of Streptococcus mitis. METHODS: Nine newborns for whom Streptococcus mitis was isolated from normally sterile sites were seen in the NICU of Eulji University Hospital from Jan. 1 to Dec. 31 2005. Medical records were reviewed for the perinatal risk factors, maternal clinical manifestations, obstetric complications and the placental pathologic findings. We also observed the neonatal clinical courses and antibiotic susceptibilities of Streptococcus mitis. RESULTS: All nine infants were high-risk newborns because of prematurity, low birth weight and/or co-morbid diseases. Clinical manifestations varied from asymptomatic to severe neonatal sepsis. Six cases resistant to ampicillin were all sensitive to vancomycin. Five among them had clinical sepsis, and one infant was asymptomatic. Three cases were sensitive to ampicillin, two of them were asymptomatic and one infant with sepsis was successfully treated with ampicillin and aminoglycoside. CONCLUSION: Streptococci mitis should not be overlooked as a contaminant when isolated from normally sterile sites. If Streptococci mitis or Viridans streptococci are recovered from a high-risk newborn showing no clinical response to penicillin, it would be better to switch antibiotics to vancomycin until the susceptibility results available.

Specific Prenatal Histories and Associated Congenital Anomalies Related to Hydronephrosis in Newborn Infants

PURPOSE: Ultrasonography is being widely used as a standard test in obstetric care, studies on congenital hydronephrosis. Focusing on specific prenatal history and frequently associated anomalies in newborn infants with hydronephrosis, this investigation was intended to suggest particulars that need to be considered in making an accurate diagnosis of fetal hydronephrosis. METHODS: From May 2000 to May 2005, retrospective study was conducted on 67 patients (93 kidney) who had been diagnosed by renal ultrasonography during neonatal periods. Hydronephrosis was defined as having a pelvic diameter more than 5 mm, and was classified into three groups according to their severity;mild (grade I, II), moderate (grade III) and severe (grade IV). RESULTS: This study included 67 cases with 54 male and 13 female infants. There were 35 cases with a specific prenatal history in 22 infants such as oligohydramnios, intrauterine growth retardation, preeclampsia and others. 33 cases in 23 infants had associated anomalies such as urogenital anomalies, cardiac anomalies. Of these 67 infants (97 kidneys), 49.5% was mild, 30.1% moderate, 20.4% severe hydronephrosis. Infants with moderate hydronephrosis had more specific prenatal history and associated anomaly than the mild hydronephrosis did (68.2% vs 31.8%, P<0.001 73.7% vs 26.3%, P<0.001). CONCLUSION: Particular attention should be paid for cases with congenital hydronephrosis with a specific prenatal history to find out any associated congenital anomalies (such as urogenital or cardiac anomalies). This will enable clinicians to establish a more appropriate treatment and postnatal care.

A Case of Suspected Fumarase Deficiency Presenting with Persistent Mild Metabolic Acidosis in Newborn Infant / 대한소아신경학회지

Fumaric aciduria(fumarase deficiency) is a rare inborn error of metabolism resulted from a deficiency of fumarase, one of the constituent enzymes of the Krebs tricarboxylic acid cycle. Enzyme deficiency causes excessive urinary excretion of fumaric acid due to a defective conversion of fumaric acid to malic acid. It usually presents early in infancy with a severe encephalopathy including hypotonia, developmental retardation and frequent seizures. We report a case of suspected fumarase deficiency presenting with persistent mild metabolic acidosis associated with moderate hydrocephalus in a newborn infant.

Acute Epididymo-orchitis in Newborn Infant

Acute scrotum in newborn infants is unusual and it is even more unusual with infectious origin. The causes of acute scrotum in newborn infants include hydrocele, testicular torsion, torsion of an appendix testis, epididymo-orchitis, meconium peritonitis, testicular tumor, scrotal hematoma and reducible or incarcerated inguinal hernia. Because of lack of typical symptoms and signs, the correct diagnosis of surgical emergencies such as testicular torsion and incarcerated inguinal hernia are often delayed. Recently, color Doppler ultrasonography and testicular scans are being used for differential diagnosis of acute scrotum, although the latter is often technically unsatisfactory due to small size of the testicles in newborn infants. We report a seven day-old male infant with acute scrotum who was diagnosed as acute epididymo-orchitis by color Doppler ultrasonography, and saved from unnecessary surgical interventions. Although color Doppler ultrasonography can not give diagnostic clue for acute scrotum, it can reduce the need for explorative surgery.

Thymus Size and its Relationship to the Respiratory Distress Syndrome and Cord Blood Cortisol Level in the Preterm Infants

PURPOSE: Thymic size can be affected by glucocorticoids which promotes surfactant synthesis in preterm infants. We assessed the hypothesis that the fetal lung maturity in preterm infant correlates with the size of the thymus detected at birth on the routine chest radiograph. We also searched for a possible relationships between thymus size, respiratory distress syndrome (RDS), and the cord blood cortisol level. METHODS: The cardiothymic/thoracic ratios (CT/T) within 6 hours after birth and cord blood cortisol levels were measured in 42 preterm infants admitted to the neonatal intensive care unit of Seoul National University Children's Hospital from June 2002 to December 2003. Multiple linear regression analyses were done to assess the relationships between the CT/T, the perinatal events and the cord blood cortisol levels. The receiver operation characteristic curve analysis was done to evaluate the CT/T in the prediction of RDS. RESULTS: 8 infants (19.0%) developed RDS. The CT/T positively correlated with the birth weight, but not with the gestational age. The CT/T were significantly larger and the cord blood cortisol levels were significantly lower in the preterm infants with RDS than in those without RDS. The cord blood cortisol levels were negatively correlated with the CT/T. The birth weight and RDS were all independently associated with the CT/T. The CT/T less than 0.37 identified infants with RDS with 87.5% sensitivity and 61.8% specificity. CONCLUSION: The larger thymus at birth can be used to identify RDS. The lower cord blood cortisol level may be associated with the larger thymus in RDS.

One Case of Systemic Lupus Erythematosus with Chief Complaint of Xerostomia and Abnormal Liver Function

Dry mouth is a common symptom in over middle- aged women. Xerostomia itself can be caused by multifactorial etiolgy. Dry mouth may occur with the use of medications, as a complication of connective tissue and autoimmune disease, such as Sjogren's syndrome or sicca syndrome, with radiation therapy to the head and neck or diabetes mellitus, or with a number of other condition. Even stress and anxiety can lead to a dry mouth. Also, Abnormal liver function is associated with drugs, viral infection, alcohol, obesity, autoimmne disease and a number of other disease. A 41-year-old women complaining of xerostomia and known abnormal liver fuction since 1 year was admitted to our medical examination center. In this case, Final diagnosis was systemic lupus erythematosus with autoimmune hepatitis and secondary Sjogren's syndrome through characteristic clinical finding, liver biopsy, positive Schirmer's test, salivary gland biopsy, and salivary scintigraphy. The various immunosuppresant medication has taken and then liver function indices and clinical symptoms were improved.

Immediate Postnatal Concentrations of Metalloproteinase-8 in the Tracheal Aspirates and the Development of Atypical Chronic Lung Disease of Prematurity

PURPOSE: Matrix metalloproteinase-8 (MMP-8) is an endoproteinase which degrades extracellular matrix and basement membrane. As early pulmonary inflammation is known to play a key role in the development of chronic lung disease (CLD), we tested the hypothesis that preterm infants who develop CLD have higher concentrations of MMP-8 in the tracheobronchial aspirates (TA) within 24 hours after birth than those who do not develop CLD. METHODS: A retrospective cohort study was done in 70 preterm infants delivered and admitted to the neonatal intensive care unit of Seoul National University Children's Hospital. TA MMP-8 concentrations were measured by ELISA. All patients were categorized into two groups according to the presence of respiratory distress syndrome (RDS). Multiple logistic regression analysis was done to assess the risk factors of CLD. RESULTS: CLD was diagnosed in 46 patients (65.7%). There were no statistically significant differences in the TA MMP-8 concentrations between CLD (+) and CLD (-)group among whole and RDS (+) groups. But in RDS (-)group, TA MMP-8 higher in CLD (+) group than in CLD (-)group. These differences persisted significantly after adjustments for the effects of gestational age at birth and histologic chorioamnionitis [P<0.050, Odds ratio: 4.720, 95% CI: 1.004-22.196]. The diagnostic indices of MMP-8 concentrations (cutoff, 7.94 ng/mL) as a predictor of development of CLD in RDS (-)group were: sensitivity of 82.4%, specificity of 77.8%, positive predictive value of 87.5%, and negative predictive value of 70.0%. CONCLUSION: There was a strong association between increased levels of TA MMP-8 and development of CLD in RDS (-)group. We propose that TA MMP-8 concentrations within 24 hours after birth may be a significant predictor of later development ofatypical CLD.

A Case of Marshall-Smith Syndrome

Marshall-Smith syndrome is characterized by a triad of facial dysmorphism, failure to thrive and accelerated osseous maturation. We report a one-month-old male infant with of this rare syndrome, with laryngeal anomalies who died at 6 months of age with pneumonia. This is the first case of Marshall-Smith syndrome in Korea.

A False Diagnosis of Hypoplastic Left Heart Syndrome in a Fetus

Typical hypoplastic left heart syndrome(HLHS) is a distinct pathologic entity with aortic atresia, mitral atresia, very hypoplastic or absent left ventricle and thread like ascending aorta. Occasionally, the lesser degree of hypoplasia is found and is called hypoplastic left heart complex(HLHC) by some authors. This HLHC is often associated with critical aortic stenosis. Fetal echocardiography has enabled us to observe human fetal heart in-utero and to diagnose congenital heart disease prenatally over the last 20 years. The diagnosis of HLHS in fetal echocardiography is based on 2-dimensional echocardio -graphic evidence of a diminutive ascending aorta, aortic atresia, mitral atresia or severe stenosis and a hypoplastic left ventricle. Abnormal flow direction through atrial septum or through isthmus greatly aids the diagnosis. This report shows a fetal case who showed hypoplastic left side chambers and retrograde isthmic flow and was diagnosed with hypoplastic left heart syndrome. After birth, although the baby had tachy-dyspnea for the first 3 weeks, she finally recovered without any intervention and showed catch up growth of left side chambers. This case illustrates the extreme difficulty of assessing left ventricle in a fetus.

Clinical Manifestations of Group A beta-Hemolytic Streptococcal Pharyngits and Usefulness of Rapid Antigen Test

PURPOSE: Accurate diagnosis of group A streptococcal(GAS) pharyngitis and appropriate antimicrobial therapy are important, particularly to prevent nonsuppurative sequelae and to reduce the improper use of antibiotics. Because the clinical presentation of pharyngitis does not reliably predict the etiologic agent, when GAS infection is suspected, diagnosis should be based on the result of a throat swab culture or antigen-detection test with culture back-up. METHODS: We reviewed retrospectively the medical records of children diagnosed as GAS pharyngitis by throat swab culture from Jan. 1995 to Jul. 2000. Since Nov. 1998, specimens were also tested with the Abbott's Testpack+plus Strep A Kit. RESULTS: 121 patients were confirmed as GAS pharyngitis by throat culture. GAS pharyngitis predominantly occurred from 3 to 7 years of age with the peak incidence at 4 and 5 years of age. The disease was more frequent in late fall, winter and spring. Clinical manifestations were as follows; fever(89.9%), abnormal pharynx(94.3%), of which exudate in 33.6%, sore throat(85.3%), headache(78.1%), cervical lymphadenopathy(67.5%), abdominal pain(64.3%), and nausea or vomiting (55.0%). The sensitivity and specificity of rapid antigen test compared to throat culture were 96.4% and 95%, respectively. CONCLUSION: GAS pharyngitis occurred every year, and more frequently in late fall, winter and spring. It occurred with the greatest frequency in preschool children. The rapid antigen test can be a basis for clinicians to decide how to treat their patients before the culture results are proven, and can be helpful to judicious use of antibiotics as well.