Case Report of Lethal Perinatal Hypophosphatasia with Seizure and Respiratory Failure Diagnosed by ALPL Gene Mutation

Hypophosphatasia is a rare disease characterized by defective bone mineralization due to deficiency of tissue-nonspecific alkaline phosphatase. The patient was an 8-day-old male infant who presented with seizure since that day. Other symptoms included res piratory failure, requiring the use of a mechanical ventilator. Physical exami na tion revealed a large bulging anterior fontanelle, soft skull bone, and radial devia tion of both wrists. Laboratory examination showed normal serum calcium, low para thyroid hormone, normal 25-hydroxy vitamin D, and severely low alkaline phos phatase levels. Skeletal X-ray revealed dysplasia of the skull and cupping of the epiphysis of the limbs. Two heterozygous mutations (c.1052A>G, c.1559delT) of the ALPL gene were identified by Sanger sequencing. Thus, we report a case of confirmed lethal perinatal hypophos phatasia in Korea.

Two Cases of Vaccine-Associated Measles in Daegu, South Korea, 2019

Korea was verified as a measles-free country by the World Health Organization in 2014;however, some imported measles cases and related outbreaks were reported. As the incidence of wild-type measles decreases in measles-free countries, the proportion of vaccine-associated measles is increasing. Wild-type measles is highly contagious and requires follow-up and management of the contacts, whereas vaccine-related measles is not contagious and does not require follow-up intervention. Therefore, measles genotyping should be performed to reliably distinguish between them in suspected patients. Two patients with vaccine-associated measles were confirmed through genotyping at Daegu Fatima Hospital. In Korea, there are only a few reports of vaccine-associated measles confirmed through genotyping; thus, we report recent vaccine-associated measles cases, emphasizing the need for genotyping.

Two Cases of Vaccine-Associated Measles in Daegu, South Korea, 2019

Korea was verified as a measles-free country by the World Health Organization in 2014;however, some imported measles cases and related outbreaks were reported. As the incidence of wild-type measles decreases in measles-free countries, the proportion of vaccine-associated measles is increasing. Wild-type measles is highly contagious and requires follow-up and management of the contacts, whereas vaccine-related measles is not contagious and does not require follow-up intervention. Therefore, measles genotyping should be performed to reliably distinguish between them in suspected patients. Two patients with vaccine-associated measles were confirmed through genotyping at Daegu Fatima Hospital. In Korea, there are only a few reports of vaccine-associated measles confirmed through genotyping; thus, we report recent vaccine-associated measles cases, emphasizing the need for genotyping.

Successful Treatment in a Newborn Infant with Chylous Ascites and Chylous Hydrocele

Chyle only occurs in the peritoneal cavity or around the pericardium through damage to the lymph nodes or improper drainage of the lymph and is characterized by a colostrum-like color and being rich in triglyceride. We encountered a case of a newborn infant with abdominal distention and further diagnosed chylous ascites and hydrocele by inspecting and analyzing the fluid obtained from the abdominal cavity and scrotum. Additionally, a lymphoscintigraphy was performed, which showed a decrease in the uptake of radioactive isotopes in the left iliac nodes and a delayed appearance. Here, we report a case of chyle diagnosed through puncture analysis and its subsequent successful treatment.

A novel mutation in the DAX1 gene in a newborn with adrenal hypoplasia congenita in Korea

Adrenal hypoplasia congenita (AHC) is a rare cause of adrenal insufficiency during neonatal period. Mutations in the gene coding for DAX1 cause X-linked adrenal hypoplasia. Most affected patients are shown to have salt wasting and hyperpigmentation on the skin during the neonatal period and require intensive medical care. In addition, it is usually associated with hypogonadotropic hypogonadism in adolescence. The DAX1 gene is expressed in the adrenal cortex, pituitary gland, hypothalamus, testis, and ovary. We report on a patient with genetically confirmed AHC whose initial clinical presentations were consistent with congenital adrenal hyperplasia. A point mutation in the DAX1 gene identified in this report resulted in a truncated DAX1 protein. Our patient was diagnosed with AHC.

Causes and Clinical Features of Transient Hypocalcemia in Newborn: A Single Center Study

PURPOSE: To review clinical symptoms, laboratory findings, and treatment of transient neonatal hypocalcemia. METHODS: Medical records of full-term (gestational age ≥37 weeks) neonates diagnosed with hypocalcemia, aged 8 mg/dL. Relative hypoparathyroidism was defined as hypocalcemia and hyperphosphatemia with parathyroid hormone level within the normal range (10–65 pg/mL). RESULTS: Of 68 included neonates, 62 were diagnosed with hypoparathyroidism with hypocalcemia and hyperphosphatemia, and 26 had seizures. Mean serum calcium level of the seizure group was 5.99 mg/dL, which was significantly lower than that of the non-seizure group (6.46 mg/dL, P=0.012). The recovery duration for calcium and phosphate levels was long, at 5.8 and 10.7 days, respectively. The calcium level recovery duration was significantly different between the seizure and non-seizure groups (P=0.034), but the phosphate level recovery period was not significantly different (P=0.194). Of 17 patients with diarrhea, 10 had confirmed rotavirus infection. Most patients with hypocalcemia responded well to oral calcium lactate and intravenous calcium gluconate, and the treatments could be discontinued after a certain period. CONCLUSION: Transient neonatal hypocalcemia is associated with hypoparathyroidism. The major symptom in late neonatal hypocalcemia was the occurrence of seizures. Serum calcium level was lower and the recovery period was longer in the seizure group, but most cases exhibited favorable progress.

Clinical Characteristics of Acute Respiratory Tract Infections in Full-Term Newborns without Risk Factors

PURPOSE: This study evaluated the characteristics and symptoms of full-term newborns without risk factors who were diagnosed with acute lower respiratory tract infections (ALRI). METHODS: Nasopharyngeal aspirates were obtained from 72 full-term newborns to 30 days of age who were diagnosed with ALRI from September 2011 to November 2013 and analyzed by multiplex real time-polymerase chain reaction (RT-PCR). RESULTS: Viruses were detected in 60 newborns (83.3%). Single viruses were observed in 56 newborns (77.7%). The most commonly detected viral agent was respiratory syncytial virus (RSV) (63.8%), followed by parainfluenza virus (6.9%), rhinovirus A/B (4.1%), and human coronavirus (2.7%). Clinical diagnoses of ALRI in newborns with a single virus included pneumonia (66.07%), bronchiolitis (30.43%), bronchitis (5.35 %), and croup (1.79%). There were no differences in epidemiological characteristics between RSV and other viruses. However, newborns diagnosed with RSV had prolonged hospitalizations and significantly increased respiratory rates. CONCLUSION: Respiratory viruses, especially RSV, are pivotal causes of ALRI in newborns. Further, studies on RSV severity and vaccination are necessary to reduce hospitalization and mortality of full-term infants.

A Novel MUT Gene Mutation Detected in a Female Infant with Methylmalonic Acidemia

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disease. MMA results from a deficiency of L-methylmalonyl-CoA mutase (encoded by MUT), its cofactor 5-deoxyadenosylcobalamin (MMAA, MMAB, and MMADHC), or a deficiency of methylmalonyl CoA-epimerase (MCEE). We report the case of a 5-day-old infant with MMA in which a missense and a novel nonsense mutation in MUT were present. Direct sequencing analysis of MUT revealed a heterozygous c.1106G>A (p.Arg369His) mutation in exon 6 and a heterozygous c.362_368dupAGTTCTA (p.Tyr123*) mutation in exon 2; the latter results in a premature stop codon.

Parotid sialolithiasis in a two-year-old boy / 소아과

Sialolithiasis is caused by the obstruction of a salivary gland or its excretory duct by the formation of calcareous concretions or sialoliths; this results in salivary ectasia and provokes subsequent dilation of the salivary gland. Sialolithiasis is relatively common, accounting for 30% of salivary diseases; however, it is rarely observed in childhood. This case report describes a 2-year-old male patient who complained of a painful swelling over the right cheek, and presented with palpable stones and pus discharge from the orifice of the right Stensen's duct. Computerized tomography of the neck confirmed the diagnosis, and the patient received intravenous empiric antibiotics combined with intraoral sialolithotomy. We also provide a review of the spectrum of concepts regarding the pathogenesis, diagnosis, and treatment of sialolithiasis.

A Case of Hemolytic Disease of a Newborn by an Anti-Di(a) Antibody Treated with Intravenous Immunoglobulin / 영남의대학술지

Hemolytic disease in a newborn that causes early jaundice is common. It is often due to the Rh (D) and ABO incompatibility, but rarely due to unexpected antibodies. Among these unexpected antibodies, the anti-Di(a) antibody rarely occurs. The anti-Di(a) antibody was observed in the serum and red-cell eluate of an infant, and in the serum of his mother. The frequency of the appearance of the Di(a) antigen in the Korean population is estimated to be 6.4-14.5%. This paper reports a case of hemolytic disease in a newborn associated with the anti-Di(a) antibody. A full-term male infant was transferred to the authors' hospital due to hyperbilirubinemia the day after his birth. The laboratory data indicated a hemoglobin value of 11.6 g/dL, a reticulocyte count of 10.6%, a total bilirubin count of 14.4 mg/dL, a direct bilirubin count of 0.6 mg/dL, and a positive result in the direct Coombs' test. Due to the identification of an irregular antibody from the maternal serum, an anti-Di(a) antibody was detected, which was also found in the eluate made from the infant's blood. The infant had been treated with phototherapy and intravenous immunoglobulin since the second day after his birth and was discharged due to an improved condition without exchange transfusion. Therefore, in cases of iso-immune hemolytic disease in a newborn within 24 hours from birth who had a negative result in an antibody screening test, the conduct of an anti-Di(a) antibody identification test is recommended due to the suspicion of an anti-Di(a) antigen, followed by early administration of intravenous immunoglobulin.

Safety and Reactogenicity of the Inactivated Poliomyelitis Vaccine (Poliorix(TM)) in Korea (2006-2012) / 소아감염

OBJECTIVE: As per the requirement of Korean Food and Drug Administration, this post-marketing surveillance was conducted in Korea to evaluate the safety and reactogenicity of Poliorix(TM) following its introduction in 2006. METHODS: In this open, multicenter study, the vaccine was administered as per the current practice of Korean doctors and in reference to the guidebook by the Korean Pediatric Society and as indicated in the Korean label which was as follows - for primary vaccination three doses were given to infants at ages 2, 4 and 6 months whereas, for the booster dose a single dose was given to children aged 4-6 years. Safety data during this six year surveillance was collected using diary cards which were distributed to the parents to record adverse events. RESULTS: A total of 639 subjects were enrolled into the study. Of these, 617 subjects and 22 subjects received the vaccine as a primary and booster dose, respectively. At least one unsolicited symptom was reported in 11.4% (73/639) of the subjects during the 7-day follow-up period; upper respiratory tract infection (2.5%;16/639) was the most frequently reported unsolicited symptom. One subject reported at least one unsolicited symptom (gastroenteritis) of grade 3 intensity within the 31-day post-vaccination period. Approximately 1.7% (11/639) of subjects reported 13 serious adverse events (SAEs). All SAEs were resolved by the end of the study. CONCLUSION: In Korea, primary and booster vaccination with Poliorix(TM) was well-tolerated in healthy subjects when administered according to the prescribing information as part of routine clinical practice.

Presumptive Diagnosis of Mycoplasma pneumoniae Pneumonia in Children / 영남의대학술지

BACKGROUND: As Mycoplasma pneumoniae pneumonia has increased in Korea, its relevance to infants, toddlers, and adolescents has magnified as well as. However, it is difficult to perform the serological test and PCR test routinely for diagnosis in actual clinical practice. Thus, the authors conducted this study to help clinicians do presumptive diagnosis of Mycoplasma pneumoniae pneumonia using clinical, radiological, and hematological findings. METHODS: The study population consisted of 224 children between 1 month and 14 years old, hospitalized for radiographically confirmed pneumonia. Patients were divided into two groups of 100 children with Mycoplasma pneumoniae pneumonia, as diagnosed using the ELISA method. Groups with negative result in Mycoplasma IgM antibody test were classified into the viral group (98 patients with respiratory virus) and the bacterial group (46 patients with the bacteria detected in the blood sputum culture or antibiotic treatment except macrolide improved the patient's condition). These groups were compared and analyzed using clinical, hematological,and radiographic differences and scoring system. RESULTS: Clinical, hematological, and radiographic characteristics of Mycoplasma pneumoniae pneumonia have shown the intermediate level results between bacterial pneumonia and viral pneumonia. In terms of scoring system, the mean score of Mycoplasma pneumoniae pneumonia was 4.23, which was the intermediate level between bacterial pneumonia (mean score=6.67) and viral pneumonia (mean score=1.48). CONCLUSION: Results suggest that the combination of the scoring system information can increase the accuracy in the diagnosis even if they may have difficulties on diagnosis, because clinical manifestations, hematological, and radiographic findings are nonspecific.

Clinical and Laboratory Finding of the 2009 Pandemic influenza A (H1N1) in Children / 소아감염

PURPOSE: 2009 Pandemic influenza A (H1N1) virus was identified in March 2009 and subsequently caused worldwide outbreaks. We described the clinical and epidemiological characteristics of H1N1 influenza infection. METHODS: We used retrospective medical chart reviews to collect data on the visiting patients from a single institute. H1N1 infection was confirmed in specimens with the use of a RT-PCR (real time reverse transcriptase polymerase chain reaction assay). RESULTS: 6,836 patients had H1N1 RT-PCR test, and 2,781 were confirmed with H1N1 virus infection. 158 patients (5.7%) had hospital treatment and inpatients were significantly younger (5.4+/-3.3 years) than outpatients (7.5+/-3.9 years) among H1N1 virus confirmed patients. Oxygen, steroid, immunoglobulin, ventilator treatment was provided in a substantial proportion among pneumonia patients accompanying wheezy respiration. In addition more intensive care was needed in patients accompanying segmental, lobar, interstitial, mixed pneumonia and lung effusion (27.2%) than patients with bronchopneumonia (7.3%) among H1N1 virus infection confirmed patients. Seventy-one infants had oseltamivir treatment out of 83 infants under 1 year, and no significant side effects and complications were identified. CONCLUSION: In 2009 pandemic influenza A (H1N1), hospital treatment was needed in younger patients. Early intensive care was needed in pneumonia patients accompanying wheezy respiration, and patients accompanying segmental, lobar, interstitial, mixed pneumonia and lung effusion.

A Novel Argininosuccinate Synthetase Gene Mutation in a Korean Family with Type I Citrullinemia

Citrullinemia type I is an urea cycle defect caused by mutations in the argininosuccinate synthetase (ASS1) gene. We report a novel argininosuccinate synthetase gene mutation in a Korean family with type I citrullinemia. Metabolic evaluation revealed significant hyperammonemia. Amino acid/acylcarnitine screening using tandem mass spectrometry showed high level of citrulline. Plasma amino acid analysis showed high level of citrulline and the urine organic acid analysis showed makedly increased level of orotic acid. To confirm diagnosis of citrullinemia we did mutation analysis of the ASS1 gene. The patient was found to have mutations of c.689G>C (p.G230A) and c.892G>A (p.E298K), which were new types of argininosuccinate synthetase gene mutation have never been reported in Korea. We report a novel case of argininosuccinate synthetase 1 gene mutation and suggest that the gene study to the family members is necessary to carry out when a patient is diagnosed as citrullinemia.

A Novel Argininosuccinate Synthetase Gene Mutation in a Korean Family with Type I Citrullinemia

Citrullinemia type I is an urea cycle defect caused by mutations in the argininosuccinate synthetase (ASS1) gene. We report a novel argininosuccinate synthetase gene mutation in a Korean family with type I citrullinemia. Metabolic evaluation revealed significant hyperammonemia. Amino acid/acylcarnitine screening using tandem mass spectrometry showed high level of citrulline. Plasma amino acid analysis showed high level of citrulline and the urine organic acid analysis showed makedly increased level of orotic acid. To confirm diagnosis of citrullinemia we did mutation analysis of the ASS1 gene. The patient was found to have mutations of c.689G>C (p.G230A) and c.892G>A (p.E298K), which were new types of argininosuccinate synthetase gene mutation have never been reported in Korea. We report a novel case of argininosuccinate synthetase 1 gene mutation and suggest that the gene study to the family members is necessary to carry out when a patient is diagnosed as citrullinemia.

Clinical Features and Risk Factors of Perinatal Hemorrhagic Stroke / 대한주산의학회잡지

OBJECTIVE: Perinatal hemorrhagic stroke (PHS) is common cause of cerebral palsy, congenital hemiparesis, and subsequent behavioral, cognitive, and language problems. Despite of this importance, risk factors for this condition have not been studied. This study was undertaken to survey the clinical features and risk factors of PHS. METHODS: A retrospective study was carried out on 24 newborns with PHS who were admitted to the neonatal intensive care unit (NICU) of Daegu Fatima hospital from January 2004 to July 2009. Cases of PHS in neonates (28 weeks' gestational age through 28 days of life) were identified through neuroimaging studies, clinical findings and chart review. Two controls per case were randomly selected. Risk factors of PHS were assessed and clinical features of PHS were reviewed. RESULTS: We identified 24 cases of PHS (19 intracerebral hemorrhage, 4 intracerebral hemorrhage with subarachnoid hemorrhage, 1 subarachnoid hemorrhage). PHS was more common in male (15 males and 9 females). Case presented with encephalopathy (100%), seizures (20.8%) and cyanosis (4.2%). The neuroimaging findings of PHS were more commonly unilateral (78.3%), and right-hemisphere (73.9%). PHS was most often seen in temporal lobe (38.2%). There were no statistical and significant risk factors of PHS. CONCLUSIONS: Newborns with PHS typically present with encephalopathy (lethargy, hypotonia, apnea, feeding disability) and seizures. The neuroimaging findings were more commonly unifocal, unilateral and seen in temporal lobe. Additional prospective studies are needed to determine the prevalence and risk factors of PHS.

The risk factors and prognosis associated with neonatal pulmonary hemorrhage / 소아과

PURPOSE: Although neonatal pulmonary hemorrhage is rare, it is associated with high mortality. We aimed to evaluate the risk factors associated with pulmonary hemorrhage in preterm infants and to describe the clinical course, including neonatal morbidity, of infants who developed pulmonary hemorrhage. METHODS: We performed a retrospective case-control study of 117 newborn infants aged less than 37 gestational weeks admitted to the neonatal intensive care unit of Daegu Fatima Hospital between January 1995 and December 2008. Control group infants without pulmonary hemorrhage were matched according to the gestational age, duration of mechanical ventilation, and birth weight range (< or =100 g). Pulmonary hemorrhage was defined as the presence of hemorrhagic fluid in the trachea and severe respiratory decompensation. RESULTS: Pulmonary hemorrhage occurred in 17 cases of very low birth weight infants (VLBW; birth weight < 1,500 g; median age, 3 days) and 22 cases of low birth weight infants (LBW; 1,500 g < or = birth weight < 2,500 g; median age, 1 day). Antenatal maternal glucocorticoid treatment significantly reduced the incidence of pulmonary hemorrhage in VLBW infants. Low APGAR score (< or =3 at 1 min) and acidosis at birth were associated with significantly high incidence of pulmonary hemorrhage in LBW infants. CONCLUSION: Antecedent factors and timing of pulmonary hemorrhage of LBW infants were different from those of VLBW infants. The mortality rates of VLBW and LBW infants were 88.2% and 45.5%, respectively. Pulmonary hemorrhage was the principal cause of death in 66.6% VLBW infants and 40.0% LBW infants.

Usefulness of auditory brainstem response as early predictor of kernicterus in early breast-feeding jaundice / 소아과

PURPOSE: The present study examined the etiology and risk factors of the early breast-feeding jaundice and the usefulness of auditory brainstem response test as early predictor of kernicterus. METHODS: Medical records of neonatal jaundice in newborn admitted to Daegu Fatima Hospital between September 2005 and May 2006 were analyzed prospectively. Infants were grouped according to feeding method:breast feeding group (breast feeding only, n=23), mixed feeding group (breast feeding mainly plus addition of fomula feeding, n=13). RESULTS: There were no significant differences in gestational age, birth weight, sex, duration of phototherapy, serum bilirubin and hemolytic evidence between the two study groups. First visiting day of life at out patient department was significantly delayed in breast feeding group (8.7+/-3.6 day) compared to mixed feeding group (6.0+/-1.9) (P=0.009). Weight loss was significantly severe in breast feeding group compared to mixed feeding group (P<0.05). In auditory brainstem response test, loss of Wave V in 3 cases was observed and recoverd after blood exchange transfusion in follow up test. Wave III latency had significant correlation to serum bilirubin in auditory brainstem response test (70 dB) (P=0.002). CONCLUSION: Our study suggest that further education about breast feeding and follow up within the first postnatal week would be necessary for early detection and prevention of early breast-feeding jaundice. Test of serum bilirubin and auditory brainstem response would be helpful in determination of blood exchange transfusion.

A Case of Cornelia de Lange Syndrome with Imperforate Anus

Cornelia de Lange syndrome is characterized by severe growth and mental retardation, characteristic face, and a low-pitched, weak, growling cry, which was first described by Cornelia de Lange in 1933. We have recognized Cornelia de Lange syndrome with imperforate anus in a male neonate. The patient had the typical facial appearance: micrognathia, confluent eyebrows, long curly eyelashes, underdeveloped orbital arches, long philtrum, thin lip, downturned angles of the mouth, anteverted nares, low-set ears, high-arched palate, and generalized hirsutism. His karyotype was normal, but skeletal abnormalities of the hands, cryptorchism, and imperforate anus with rectourethral fistula. A colostomy was performed on the third day of hospitalization.

A Fatal Case of Severe Hemolytic Disease of Newborn Associated with Anti-Jk(b)

The Kidd blood group is clinically significant since the Jk antibodies can cause acute and delayed transfusion reactions as well as hemolytic disease of newborn (HDN). In general, HDN due to anti-Jk(b) incompatibility is rare and it usually displays mild clinical symptoms with a favorable prognosis. Yet, we apparently experienced the second case of HDN due to anti-Jk(b) with severe clinical symptoms and a fatal outcome. A female patient having the AB, Rh(D)-positive boodtype was admitted for jaundice on the fourth day after birth. At the time of admission, the patient was lethargic and exhibited high pitched crying. The laboratory data indicated a hemoglobin value of 11.4 mg/dL, a reticulocyte count of 14.9% and a total bilirubin of 46.1 mg/dL, a direct bilirubin of 1.1 mg/dL and a strong positive result (+++) on the direct Coomb's test. As a result of the identification of irregular antibody from the maternal serum, anti-Jk(b) was detected, which was also found in the eluate made from infant's blood. Despite the aggressive treatment with exchange transfusion and intensive phototherapy, the patient died of intractable seizure and acute renal failure on the fourth day of admission. Therefore, pediatricians should be aware of the clinical courses of hemolytic jaundice due to anti-Jk(b), and they should be ready to treat this disease with active therapeutic interventions.