Aram Yang

Acute Necrotizing Pancreatitis Associated with Mycoplasma pneumoniae Infection in a Child

Mycoplasma pneumoniae is responsible for approximately 20% to 30% of community-acquired pneumonia, and is well known for its diverse extrapulmonary manifestations. However, acute necrotizing pancreatits is an extremely rare extrapulmonary manifestation of M. pneumoniae infection. A 6-year-old girl was admitted due to abdominal pain, vomiting, fever, and confused mentality. Acute necrotizing pancreatitis was diagnosed according to symptoms, laboratory test results, and abdominal computed tomography scans. M. pneumoniae infection was diagnosed by a 4-fold increase in antibodies to M. pneumoniae between acute and convalescent sera by particle agglutination antibody assay. No other etiologic factors or pathogens were detected. Despite the occurrence of a large infected pseudocyst during the course, the patient was able to discharge without morbidity by early aggressive supportive care. This is the first case in Korea of a child with acute necrotizing pancreatitis associated with M. pneumoniae infection.

Further delineation of COG8-CDG: A case with novel compound heterozygous mutations diagnosed by targeted exome sequencing

Congenital disorders of glycosylation (CDG) are a rapidly expanding group of inherited metabolic disorders with highly variable clinical presentations caused by deficient glycosylation of proteins and/or lipids. CDG-IIh is a very rare subgroup of CDG caused by mutations in the conserved oligomeric Golgi (COG) complex gene, COG8, and so far, only two cases have been reported in the medical literature. Here, we describe an 8-year-old Korean boy with psychomotor retardation, hypotonia, failure to thrive, elevated serum liver enzymes, microcephaly, and talipes equinovarus. A liver biopsy of the patient showed only interface hepatitis with mild lobular activity, and brain magnetic resonance imaging revealed cerebellar atrophy. Compared with the previous two reported cases, our patient showed relatively mild psychomotor retardation without a seizure history. The transferrin isoelectric focusing profiles in the patient showed a CDG type II pattern with increased disialo- and trisialo-transferrin. Targeted exome sequencing was performed to screen all CDG type II-related genes, and two novel frameshift mutations were found: c.171dupG (p.Leu58Alafs*29) and c.1656dupC (p.Ala553Argfs*15) in COG8. The parents were heterozygous carriers of each variant. CDG should be included in the initial differential diagnosis for children with a suspected unknown syndrome or unclassified inherited metabolic disorder or children with diverse clinical presentations, such as psychomotor retardation, hypotonia, skeletal deformity, microcephaly, cerebellar atrophy, and unexplained transient elevated liver enzyme.

2q37 Deletion syndrome confirmed by high-resolution cytogenetic analysis

Chromosome 2q37 deletion syndrome is a rare chromosomal disorder characterized by mild to moderate developmental delay, brachydactyly of the third to fifth digits or toes, short stature, obesity, hypotonia, a characteristic facial appearance, and autism spectrum disorder. Here, we report on a patient with 2q37 deletion presenting with dilated cardiomyopathy (DCMP). Congenital heart malformations have been noted in up to 20% of patients with 2q37 deletions. However, DCMP has not been reported in 2q37 deletion patients previously. The patient exhibited the characteristic facial appearance (a flat nasal bridge, deep-set eyes, arched eyebrows, and a thin upper lip), developmental delay, mild mental retardation, peripheral nerve palsy, and Albright hereditary osteodystrophy (AHO)-like phenotypes (short stature and brachydactyly). Conventional chromosomal analysis results were normal; however, microarray-based comparative genomic hybridization revealed terminal deletion at 2q37.1q37.3. In addition, the patient was confirmed to have partial growth hormone (GH) deficiency and had shown a significant increase in growth rate after substitutive GH therapy. Chromosome 2q37 deletion syndrome should be considered in the differential diagnosis of patients presenting with AHO features, especially in the presence of facial dysmorphism. When patients are suspected of having a 2q37 deletion, high-resolution cytogenetic analysis is recommended.

Clinical and molecular characterization of Korean children with infantile and late-onset Pompe disease: 10 years of experience with enzyme replacement therapy at a single center

Purpose Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of acid alphaglucosidase resulting from pathogenic GAA variants. This study describes the clinical features, genotypes, changes before and after enzyme replacement therapy (ERT), and long-term outcomes in patients with infantile-onset PD (IOPD) and late-onset PD (LOPD) at a tertiary medical center. Methods The medical records of 5 Korean patients (2 male, 3 female patients) diagnosed with PD between 2002 and 2013 at Samsung Medical Center in Seoul, Republic of Korea were retrospectively reviewed for data, including clinical and genetic characteristics at diagnosis and clinical course after ERT. Results Common initial symptoms included hypotonia, cyanosis, and tachycardia in patients with IOPD and limb girdle weakness in patients with LOPD. Electrocardiography at diagnosis revealed hypertrophic cardiomyopathy in all patients with IOPD who showed a stable disease course during a median follow-up period of 10 years. Patients with LOPD showed improved hepatomegaly and liver transaminase level after ERT. Conclusion As ERT is effective for treatment of PD, early identification of this disease is very important. Thus, patients with IOPD should be considered candidates for clinical trials of new drugs in the future.

Etiological trends in male central precocious puberty

Purpose In the present study, the etiological trends in male central precocious puberty (CPP) were examined, and annual distribution was evaluated. Methods Seventy-one male CPP subjects who started puberty before 9 years of age were included in this study. All individuals were diagnosed as having CPP at Samsung Medical Center between 2001 and 2016. Chronological age at puberty onset, diagnosis of CPP, bone age, weight (kg), height (cm), puberty stage, brain magnetic resonance imaging findings, testosterone level, basal gonadotropin level, and gonadotropin level after gonadotropin releasing hormone stimulation were analyzed. Results The 71 patients were divided into 2 groups: idiopathic (group I) and organic (group II) when the lesion was identified as associated with the central nervous system (CNS) or when the patient received chemotherapy for non-CNS tumors before CPP diagnosis, respectively. Forty-four cases (62%) were idiopathic, and 27 (38%) were organic. The proportion of idiopathic CPP was higher than that of organic CPP during the study period. In 51.9% of organic cases, puberty started before 8 years of age, whereas it started after that age in 93.2% of the idiopathic cases. Conclusions In the present study, among all male CPP cases, 62% were idiopathic. The probability of idiopathic CPP prevalence was higher in males when the puberty onset was after 8 years of age with no history of cranial radiotherapy or chemotherapy.

Prevalence and Epidemiological Characteristics of Endoscopically Proven Reflux Esophagitis in Children in Korea

Purpose The prevalence of reflux esophagitis (RE) has increased recently in Korea. Little is known concerning the prevalence and characteristics of RE in pediatric patients. This study investigated the prevalence and influence of risk factors in endoscopically proven RE in Korea in pediatric patients over a period of 14 years. Methods A retrospective chart review of all patients between the ages of 1 month and 20 years who underwent esophagogastroduodenoscopy at Samsung Medical Center between 2001 and 2014 was carried out. Univariate and multivariate analyses were conducted to identify independent risk factors for RE. Results The prevalence rate of endoscopically proven RE in this study was 28.7% (978/3,413). The prevalence of RE increased from 11.8% from 2001 to 2007 to 37.7% from 2008 to 2014. Multivariate logistic regression analysis revealed that residency in the Greater Gangnam area (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.02-1.44) and age (OR, 1.13; 95% CI, 1.11-1.15) were significant predictive factors for the presence of RE. Conclusion The prevalence rate of endoscopically proven pediatric RE has increased over the past 14 years. Residency and older age are more important independent risk factors for pediatric RE in Korea.

HDR syndrome with a novel mutation in GATA3 mimicking a congenital X-linked stapes gusher: a case report

BackgroundHypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome, also known as Barakat syndrome, is a rare genetic disorder with high phenotypic heterogeneity caused by haploinsufficiency of the GATA3 gene on chromosome 10p14-p15. For these reasons, the diagnosis of HDR syndrome is challenging and requires a high index of suspicion as well as genetic analysis.Case presentationA 14-month-old boy, with sensorineural hearing loss in both ears, showed typical radiological features of X-linked stapes gusher on preoperative temporal bone computed tomography (CT) for cochlear implantations. Then after his discharge from hospital, he suffered a hypocalcemic seizure and we discovered a renal cyst during investigation of hypocalcemia. He was finally diagnosed with HDR syndrome by clinical findings, which were confirmed by molecular genetic testing. Direct sequencing of the GATA3 gene showed a heterozygous 2-bp deletion (c.1201_1202delAT), which is predicted to cause a frameshift of the reading frame (p.Met401Valfs*106).ConclusionsTo our knowledge, this is the first case of HDR syndrome with a novel de novo variant mimicking a congenital X-linked stapes gusher syndrome. Novel mutations and the diversity of clinical manifestations expand the genotypic and phenotypic spectrum of HDR syndrome.Diagnosis of HDR syndrome is still challenging, but clinicians should consider it in their differential diagnosis for children with a wide range of clinical manifestations including hypocalcemia induced seizures and deafness. We hope that this case will contribute to further understanding and studies of HDR-associated GATA3 mutations.

An atypical case of Noonan syndrome with KRAS mutation diagnosed by targeted exome sequencing

Noonan syndrome (NS) is a genetic disorder caused by autosomal dominant inheritance and is characterized by a distinctive facial appearance, short stature, chest deformity, and congenital heart disease. In individuals with NS, germline mutations have been identified in several genes involved in the RAS/mitogen-activated protein kinase signal transduction pathway. Because of its clinical and genetic heterogeneity, the conventional diagnostic protocol with Sanger sequencing requires a multistep approach. Therefore, molecular genetic diagnosis using targeted exome sequencing (TES) is considered a less expensive and faster method, particularly for patients who do not fulfill the clinical diagnostic criteria of NS. In this case, the patient showed short stature, dysmorphic facial features suggestive of NS, feeding intolerance, cryptorchidism, and intellectual disability in early childhood. At the age of 16, the patient still showed extreme short stature with delayed puberty and characteristic facial features suggestive of NS. Although the patient had no cardiac problems or chest wall deformities, which are commonly present in NS and are major concerns for patients and clinicians, the patient showed several other characteristic clinical features of NS. Considering the possibility of a genetic disorder, including NS, a molecular genetic study with TES was performed. With TES analysis, we detected a pathogenic variant of c.458A > T in KRAS in this patient with atypical NS phenotype and provided appropriate clinical management and genetic counseling. The application of TES enables accurate molecular diagnosis of patients with nonspecific or atypical features in genetic diseases with several responsible genes, such as NS.

Birth seasonality in Korean Prader-Willi syndrome with chromosome 15 microdeletion

Purpose Prader-Willi syndrome (PWS) is a well-known genetic disorder, and microdeletion on chromosome 15 is the most common causal mechanism. Several previous studies have suggested that various environmental factors might be related to the pathogenesis of microdeletion in PWS. In this study, we investigated birth seasonality in Korean PWS. Methods A total of 211 PWS patients born from 1980 to 2014 were diagnosed by methylation polymerase chain reaction at Samsung Medical Center. Of the 211 patients, 138 were born from 2000-2013. Among them, the 74 patients of a deletion group and the 22 patients of a maternal uniparental disomy (UPD) group were compared with general populations born from 2000 using the Walter and Elwood method and cosinor analysis. Results There was no statistical significance in seasonal variation in births of the total 211 patients with PWS (χ2=7.2522, P=0.2982). However, a significant difference was found in the monthly variation between PWS with the deletion group and the at-risk general population (P<0.05). In the cosinor model, the peak month of birth for PWS patients in the deletion group was January, while the nadir occurred in July, with statistical significance (amplitude=0.23, phase=1.2, low point=7.2). The UPD group showed the peak birth month in spring; however, this result was not statistically significant (χ2=3.39, P=0.1836). Conclusion Correlation with birth seasonality was identified in a deletion group of Korean PWS patients. Further studies are required to identify the mechanism related to seasonal effects of environmental factors on microdeletion on chromosome 15.