Purpose: Whole-exome sequencing (WES) has been a useful tool for novel gene discovery of various disease categories, further increasing the diagnostic yield. This study aimed to investigate the clinical utility of WES prospectively in undiagnosed genetic diseases. Materials and Methods: WES tests were performed on 110 patients (age range, 0-28 years) with suspected rare genetic diseases. WES tests were performed at a single reference laboratory and the variants reported were reviewed by clinical geneticists, pediatricians, neurologists, and laboratory physicians. Results: The patients’ symptoms varied with abnormalities in the head or neck, including facial dysmorphism, being the most common, identified in 85.4% of patients, followed by abnormalities in the nervous system (83.6%). The average number of systems manifesting phenotypic abnormalities per patient was 3.9±1.7. The age at presentation was 2.1±2.7 years old (range, 0-15 years), and the age at WES testing was 6.7±5.3 years (range, 0-28 years). In total, WES test reported 100 pathogenic/likely pathogenic variants or variants of uncertain significance for 79 out of 110 probands (71.8%). Of the 79 patients with positive or inconclusive calls, 55 (50.0%) patients were determined to have good genotype-phenotype correlations after careful review. Further clinical reassessment and family member testing determined 45 (40.9%) patients to have been identified with a molecular diagnosis. Conclusion This study showed a 40.9% diagnostic yield for WES test for a heterogeneous patient cohort with suspected rare genetic diseases. WES could be the feasible genetic test modality to overcome the diversity and complexity of rare disease diagnostics.

Background: Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. Methods: Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years). Results: The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. Conclusion On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.

Background: Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. Methods: Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years). Results: The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. Conclusion On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.

Background: The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. Methods: This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. Results: Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53%) and infection (44%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. Conclusions Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

BACKGROUND: BRAF V600E mutation status and prevalence of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been reported in Korea. The aim of this study was to investigate the significance of the BRAF V600E mutation in the follicular variant of papillary thyroid carcinoma (FVPTC) and to determine the prevalence of NIFTP in BRAF V600E mutation-prevalent Korean patients. METHODS: This study retrospectively analyzed 1,417 consecutive patients who underwent total thyroidectomy with routine prophylactic central lymph node dissection for papillary thyroid carcinoma (PTC). BRAF V600E mutation analysis was performed routinely using multiplex polymerase chain reaction by applying dual priming oligonucleotide. Clinicopathological characteristics and ultrasonographic findings were compared between BRAF V600E mutation-positive and -negative groups for FVPTC. Pathologists reviewed the pathology slides according to consensus diagnostic criteria for the encapsulated FVPTC and NIFTP. RESULTS: The prevalence of the BRAF V600E mutation in all subtypes of PTC was 61.0% (861/1,411). FVPTC presented a BRAF V600E mutation rate of 27.3%. The FVPTC patients with BRAF V600E mutation were older than those with no BRAF V600E mutation (P = 0.021). The prevalence of NIFTP was 0.18% among all PTC patients (2/1,411) and the proportion of NIFTP among FVPTC was 9.1% (2/22). CONCLUSION: The BRAF V600E mutation is prevalent in Korean patients with FVPTC in a region with high frequency of the BRAF V600E mutation and very low prevalence of NIFTP compared with that reported in western studies.
Carcinoma, Papillary ; Consensus ; Humans ; Korea ; Lymph Node Excision ; Multiplex Polymerase Chain Reaction ; Mutation Rate ; Pathology ; Prevalence* ; Retrospective Studies ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

Leiomyosarcoma (LMS) of the small intestine is a rare tumor, accounting for about 1% of all malignant mesenchymal lesions in the gastrointestinal tract. Since small bowel tumors are initially asymptomatic and nonspecific, delayed diagnosis and treatment are common. We found that a 44-year-old male patient who came in for lower abdominal pain had partial obstruction in the small bowel. Multiple ascites and ileal tumors involving peritoneal seeding were observed from his abdominal computed tomography. He was diagnosed as epithelioid LMS involving peritoneal transition after surgical resection, and the outpatient department has planned for a conservative therapy with observation. To the best of our knowledge, ileal epithelioid LMS accompanying a huge omental mass, with a size of 18 cm in dimension, and peritoneal seeding has not yet been reported in Korea. We report this rare case with literature review.
Abdominal Pain ; Adult ; Ascites ; Delayed Diagnosis ; Gastrointestinal Tract ; Humans ; Ileum ; Intestine, Small ; Korea ; Leiomyosarcoma* ; Male ; Outpatients

Leiomyosarcoma (LMS) of the small intestine is a rare tumor, accounting for about 1% of all malignant mesenchymal lesions in the gastrointestinal tract. Since small bowel tumors are initially asymptomatic and nonspecific, delayed diagnosis and treatment are common. We found that a 44-year-old male patient who came in for lower abdominal pain had partial obstruction in the small bowel. Multiple ascites and ileal tumors involving peritoneal seeding were observed from his abdominal computed tomography. He was diagnosed as epithelioid LMS involving peritoneal transition after surgical resection, and the outpatient department has planned for a conservative therapy with observation. To the best of our knowledge, ileal epithelioid LMS accompanying a huge omental mass, with a size of 18 cm in dimension, and peritoneal seeding has not yet been reported in Korea. We report this rare case with literature review.
Abdominal Pain ; Adult ; Ascites ; Delayed Diagnosis ; Gastrointestinal Tract ; Humans ; Ileum ; Intestine, Small ; Korea ; Leiomyosarcoma ; Male ; Outpatients

BACKGROUND: Viridans streptococci (VS) are a large group of streptococcal bacteria that are causative agents of community-acquired respiratory tract infection. However, data regarding their clinical characteristics are limited. The purpose of the present study was to investigate the clinical and radiologic features of community-acquired pneumonia (CAP) with or without parapneumonic effusion caused by VS. METHODS: Of 455 consecutive CAP patients with or without parapneumonic effusion, VS were isolated from the blood or pleural fluid in 27 (VS group, 5.9%) patients. Streptococcus pneumoniae was identified as a single etiologic agent in 70 (control group) patients. We compared various clinical parameters between the VS group and the control group. RESULTS: In univariate analysis, the VS group was characterized by more frequent complicated parapneumonic effusion or empyema and bed-ridden status, lower incidences of productive cough, elevated procalcitonin (>0.5 ng/mL), lower age-adjusted Charlson comorbidity index score, and more frequent ground glass opacity (GGO) or consolidation on computed tomography (CT) scans. Multivariate analysis demonstrated that complicated parapneumonic effusion or empyema, productive cough, bed-ridden status, and GGO or consolidation on CT scans were independent predictors of community-acquired respiratory tract infection caused by VS. CONCLUSION: CAP caused by VS commonly presents as complicated parapneumonic effusion or empyema. It is characterized by less frequent productive cough, more frequent bed-ridden status, and less common CT pulmonary parenchymal lesions. However, its treatment outcome and clinical course are similar to those of pneumococcal pneumonia.
Bacteria ; Comorbidity ; Cough ; Empyema ; Glass ; Humans ; Incidence ; Methods ; Multivariate Analysis ; Pneumonia* ; Pneumonia, Pneumococcal ; Respiratory Tract Infections ; Streptococcus pneumoniae ; Tomography, X-Ray Computed ; Treatment Outcome ; Viridans Streptococci

Lidocaine is a commonly used local anesthetic for dental treatment. Urticaria caused by lidocaine has seldom been reported. Generally, urticaria immediately develops after exposure to a causative agent and is considered a manifestation of IgE-mediated hypersensitivity. However, delayed urticaria caused by local anesthetics was reported to be related to cell mediated hypersenstivity. A 3-year old girl visited our allergy clinic due to delayed urticaria after local administration of lidocaine. Both skin prick and intradermal tests with lidocaine revealed negative reactions. However, the provocation test with subcutaneous injection of lidocaine showed urticaria 7 hours after test. In order to identify alternative local anesthetic for the subsequent dental procedure, we performed skin prick, intradermal and provocation tests with procaine, a local anesthetic of the other class, all of which showed negative results. Therefore, we recommended procaine as an alternative local anesthetic, and the patient was successfully treated with procaine. To the best of our knowledge, this is the first case of delayed urticaria caused by lidocaine in Korea.
Anesthetics, Local ; Child* ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Injections, Subcutaneous ; Intradermal Tests ; Korea ; Lidocaine* ; Procaine ; Skin ; Urticaria*

PURPOSE: Allergic diseases have been increased in Korea. The aim of this study was to investigate the changes of sensitization rate to inhalant allergens over 10 years in children with allergic diseases from a tertiary referral hospital. METHODS: Skin prick tests were done in total 2,225 children in 2000, 2005, and 2010. Changes of skin reactivity to 12 major inhalant allergens, including Tree pollen mixture I (Alder, Elm, Hazel, Poplar, Willow), Tree pollen mixture II (Beech, Birch, Oak, Plane tree), Dermatophagoides pteronyssinus, Dermatophagoides farina, Alternaria, cat dander, and dog dander were investigated. RESULTS: The sensitization rates to Tree pollen mixture I and II were increased as 5.0%, 6.8% in 2000, 8.5%, 9.8% in 2005, and 14.8%, 17.3% in 2010, respectively (trend P<0.001, P<0.001, respectively). And the sensitization rates to D. pteronyssinus cat dander and dog dander were changed as 55%, 4.8%, 4.8% in 2000, 62.2%, 11.9%, 28% in 2005, and 63.1%, 12.7%, 16.7% in 2010, respectively. The distribution of sensitized pollens was oak (12.8%), beech (12.4%), pine (10.3%), birch (10%), hazel (9.6%), alder (8%), elder (6.9%), elm (5.4%) in the study of 2010. When allergen/histamine ratio was compared, rates of strong sensitization over 4+ to tree pollen were increased. CONCLUSION: The sensitization rates to inhalant allergens were increased in children with asthma or allergic rhinitis from a tertiary referral hospital in Seoul over last 10 years. Especially, an increase in the degree of skin reactivity was observed in cat dander, dog dander, and tree pollens. The studies to investigate the etiology of this increase and prevention will be needed.
Allergens ; Alnus ; Alternaria ; Animals ; Asthma* ; Betula ; Cats ; Child* ; Dander ; Dermatophagoides pteronyssinus ; Dogs ; Fagus ; Humans ; Hypersensitivity ; Korea ; Pollen ; Pyroglyphidae ; Rhinitis* ; Seoul ; Skin ; Tertiary Care Centers*