BACKGROUND: This study aimed to investigate the current statuses of eight hormone tests (testosterone, estradiol, prolactin, progesterone, luteinizing hormone, follicle-stimulating hormone, parathyroid hormone, and thyroglobulin) used by clinical laboratories in Korea. METHODS: From November 1 to December 31, 2016, we surveyed 300 laboratories that participated in the regular proficiency survey program administered by the Korean Association of Quality Assurance for Clinical Laboratory. The survey comprised a questionnaire designed to address factors related to these hormone tests, including the measurement methods, instruments, test numbers per month, turnaround times, reporting units and ranges, reference ranges, and internal or external quality control methods. RESULTS: Fifty-four (18.0%) of 300 laboratories replied to the survey questionnaire. Each laboratory performed hormone analyses that used variable instruments, commercial kits, and calibrators. The test numbers per month, turnaround times, and reporting units (particularly for testosterone) varied among laboratories. Most laboratories used reference intervals that had been transferred from other references and were verified using in-house samples. Many laboratories that assessed luteinizing hormone, follicle-stimulating hormone, and parathyroid hormone levels did not participate in the proficiency survey program conducted by The Korean Association of Quality Assurance for Clinical Laboratory. CONCLUSIONS: We hope that the results of this study, which investigated the status of hormone testing at Korean diagnostic laboratories, will facilitate improvements in the quality of hormone testing and promote the development of guidelines for testing.
Clinical Laboratory Services ; Estradiol ; Follicle Stimulating Hormone ; Hope ; Korea* ; Laboratory Proficiency Testing ; Luteinizing Hormone ; Parathyroid Hormone ; Progesterone ; Prolactin ; Quality Control ; Reference Values ; Surveys and Questionnaires

Background: Because there is limited recent information on this topic, this study investigated the seroprevalence of anti-hepatitis A virus (HAV) immunoglobulin G (IgG) in the South Korean population in 2015–2017. Methods: Anti-HAV IgG seroprevalence data were obtained from the laboratory information system of Green Cross Laboratories, one of the largest referral laboratories in South Korea. Results: During the three-year study period, we obtained test results from 240,840 individuals (124,353 men and 116,487 women) from 1,348 hospitals and local clinics throughout South Korea. The median (range) age of subjects was 38.0 (18.0–97.2) years. The annual seroprevalence of anti-HAV IgG was 53.3%, 53.0%, and 53.1% in 2015, 2016, and 2017, respectively. The median age differed among geographic regions and anti-HAV seroprevalence differed among age groups and geographic regions (P<0.0001). Subjects in their 20’s had a significantly lower rate of anti-HAV IgG-positivity than subjects in their 10’s (odds ratio, [OR] 0.74, 95% CI, 0.69–0.78, P<0.0001), while other age groups had higher rates. Multivariable-adjusted logistic regression analysis showed that women and subjects living in Inchoen, Sejong city, Gangwon province, Gwangju, and North Jeolla province were more likely to be immune to HAV compared to subjects living in Seoul (OR >1.0, P<0.05). Conclusions This study provides basic information about the recent seroprevalence of anti-HAV IgG in the Korean population and contributes to identifying groups at high risk of an HAV epidemic.

BACKGROUND: Several molecular assays have been developed to detect the BRAF V600E mutation in fine needle aspirates (FNAs) for the diagnosis of papillary thyroid cancer. Using a multiplex PCR technique, we evaluated the Anyplex BRAF V600E Real-time Detection (Anyplex) assay and compared its efficacy with that of the Seeplex BRAF V600E ACE Detection (Seeplex) method. METHODS: We tested 258 consecutive FNA specimens using the Seeplex and Anyplex assays. Any conflicting results between the two assays were confirmed by using mutant enrichment with 3'-modified oligonucleotide (MEMO) sequencing. The limits of detection (LODs) and reproducibility for each assay were evaluated with serially diluted DNA from a BRAF V600E-positive cell line. RESULTS: The BRAF V600E mutation was detected in 36.4% (94/258) FNA specimens by either the Seeplex or Anyplex assay. Results for the two assays showed 93.4% (241/258) agreement, with a kappa value of 0.861 (95% confidence interval, 0.798-0.923). Of the eight specimens that were BRAF V600E-positive by the Anyplex assay but not by the Seeplex assay, five were found to be BRAF V600E-positive by MEMO sequencing. The mutation detection rate of the Seeplex and Anyplex assays was 79.0% and 84.0%, respectively, in the FNA specimens diagnosed as malignant (n=81). The LOD as determined by probit analysis was 0.046% (95% confidence interval, 0.019-0.532%). CONCLUSIONS: The Anyplex assay performed better than the Seeplex assay with respect to the detection of the BRAF V600E mutation.
Adult ; Aged ; Asian Continental Ancestry Group/genetics ; Biopsy, Fine-Needle ; DNA/chemistry/metabolism ; DNA Mutational Analysis/*methods ; DNA Primers/*metabolism ; Female ; Humans ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction ; Oligonucleotides/metabolism ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins B-raf/*genetics ; Republic of Korea ; Thyroid Nodule/*metabolism/pathology

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.
Antitubercular Agents/blood/*therapeutic use ; Arylamine N-Acetyltransferase/genetics ; Chromatography, High Pressure Liquid ; Drug Monitoring ; Humans ; Nutritional Status ; Pharmacogenetics ; Tandem Mass Spectrometry ; Tuberculosis/*drug therapy

PURPOSE: We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant). Clinical and laboratory features during the first year of maintenance therapy were investigated. RESULTS: A total of 182 patients were included in the final analysis. There were five (2.7%), 46 (25.3%), and 131 (72.0%) patients in low-, intermediate-, and normal-activity groups, respectively. The lowest 6-mercaptopurine (6-MP) dose (mg/m2/day) was administered to the low-activity group (low-activity group 7.5 vs. intermediate-activity group 24.4 vs. normalactivity group 31.1, p < 0.01) from three months to a year after beginning maintenance therapy. The low-activity group experienced the longest duration of therapy interruption during the first year (low-activity group 169 days vs. intermediate-activity group 30 days vs. normal-activity group 16 days, p < 0.01). They also showed the lowest blood cell counts and had a longer duration of leukopenia (low-activity group 131 days vs. intermediate-activity group 92 days vs. normal-activity group 59 days, p < 0.01). 6-TGN level and its ratio to 6-MP dose were lowest in the low-activity group. CONCLUSION: NUDT15 variants cause hematopoietic toxicity with low 6-TGN levels. NUDT15 genotyping should be conducted before administering thiopurine, and dose adjustments require caution regardless of 6-TGN levels.
6-Mercaptopurine ; Blood Cell Count ; Child* ; Humans ; Leukemia ; Leukopenia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Thioguanine

Diagnosis of the urea cycle disorder (USD) carbamoyl-phosphate synthetase 1 (CPS1) deficiency (CPS1D) based on only the measurements of biochemical intermediary metabolites is not sufficient to properly exclude other UCDs with similar symptoms. We report the first Korean CPS1D patient using whole exome sequencing (WES). A four-day-old female neonate presented with respiratory failure due to severe metabolic encephalopathy with hyperammonemia (1,690 µmol/L; reference range, 11.2-48.2 µmol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 µmol/L; reference range, 131-710 µmol/L) and glutamine (5,777 µmol/L; reference range, 376-709 µmol/L), whereas that of citrulline was decreased (2 µmol/L; reference range, 10-45 µmol/L). WES revealed compound heterozygous pathogenic variants in the CPS1 gene: one novel nonsense pathogenic variant of c.580C>T (p.Gln194*) and one known pathogenic frameshift pathogenic variant of c.1547delG (p.Gly516Alafs*5), which was previously reported in Japanese patients with CPS1D. We successfully applied WES to molecularly diagnose the first Korean patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs.
Base Sequence ; Carbamoyl-Phosphate Synthase (Ammonia)/chemistry/*genetics ; Carbamoyl-Phosphate Synthase I Deficiency Disease/diagnosis/*genetics ; Codon, Nonsense ; Exons ; Female ; Frameshift Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Republic of Korea ; Sequence Analysis, DNA ; Urea Cycle Disorders, Inborn/diagnosis

No abstract available.
Adult ; Aged ; Antifungal Agents/therapeutic use ; Candida/*genetics/isolation & purification ; Candidiasis/diagnosis/drug therapy/*microbiology ; *Diagnostic Errors ; Female ; Fluconazole/therapeutic use ; Humans ; Infant ; Lymphoma, T-Cell/diagnosis/microbiology ; Male ; Reagent Kits, Diagnostic/*standards

CYP21A2 mutation analysis of congenital adrenal hyperplasia (CAH) is challenging because of the genomic presence of a homologous CYP21A2 pseudogene and the significant incidence of pseudogene conversion and large deletions. The objective of this study was to accurately analyze the CYP21A2 genotype in Korean CAH patients using a combination of complementary methods. Long-range PCR and restriction fragment length polymorphism analyses were performed to confirm valid amplification of CYP21A2 and to detect large gene conversions and deletions before direct sequencing. Multiple ligation-dependent probe amplification (MLPA) analysis was conducted concurrently in 14 CAH-suspected patients and six family members of three patients. We identified 27 CYP21A2 mutant alleles in 14 CAH-suspected patients. The c.293-13A>G (or c.293-13C>G) was the most common mutation, and p.Ile173Asn was the second, identified in 25% and 17.9% of alleles, respectively. A novel frame-shift mutation of c.492delA (p.Glu 164Aspfs*24) was detected. Large deletions were detected by MLPA in 10.7% of the alleles. Mutation studies of the six familial members for three of the patients aided in the identification of haplotypes. In summary, we successfully identified CYP21A2 mutations using both long-range PCR and sequencing and dosage analyses. Our data correspond relatively well with the previously reported mutation spectrum analysis.
Adrenal Hyperplasia, Congenital* ; Alleles ; Gene Conversion ; Genotype ; Haplotypes ; Humans ; Incidence ; Korea ; Polymerase Chain Reaction* ; Polymorphism, Restriction Fragment Length* ; Pseudogenes ; Spectrum Analysis

Metachromatic leukodystrophy is an inherited lysosomal storage disorder caused by the deficiency of arylsulfatase A activity. The patient in this study, a 5-yr-old girl, presented with progressive psychomotor regression. An MRI image of her brain showed bilateral symmetrical demyelination. The arylsulfatase A activity in her leukocytes was decreased to 8.0 nmol/hr/mg protein (reference range, 25-80 nmol/hr/mg protein). Mutation analysis of ARSA, using PCR and direct sequencing, showed two heterozygote pathogenic variations of c.449C>T (p.Pro150Leu) and c.640G>A (p.Ala214Thr). In summary, we report a Korean patient with an early juvenile form of metachromatic leukodystrophy, who was diagnosed based on her clinical symptoms as well as by using biochemical, radiological, and molecular genetic investigations.
Brain ; Cerebroside-Sulfatase ; Demyelinating Diseases ; Female ; Heterozygote ; Humans ; Leukocytes ; Leukodystrophy, Metachromatic* ; Magnetic Resonance Imaging ; Molecular Biology* ; Polymerase Chain Reaction

Apolipoprotein E (APOE) polymorphisms are used as biological markers to assess the risk of cardiovascular disease, dyslipidemia, and Alzheimer's disease. Consequently, APOE genotyping is one of the most frequently conducted tests in clinical molecular laboratories. Although APOE genotyping may appear to be uncomplicated and a relatively easy test to perform, genotyping errors can still occur due to polymorphisms near codons 112 and 158 in the human APOE gene. Therefore, validation and verification of APOE genotyping assays before clinical use are essential. So far, we have been using the TaqMan SNP Genotyping Assay (Life Technologies, USA). However, recently, the Real-Q ApoE genotyping kit (BioSewoom, Korea) was approved by the Korean Ministry of Food and Drug Safety, which led us to compare the results obtained from this genotyping kit to those of the TaqMan SNP Genotyping Assay. The Real-Q ApoE genotyping kit yielded correct genotyping results for all six APOE genotypes and provided concordant results with the TaqMan SNP Genotyping Assay in a series of blinded comparison samples. Thus, we validated its use in clinical tests.
Alzheimer Disease ; Apolipoproteins E ; Apolipoproteins* ; Biomarkers ; Cardiovascular Diseases ; Codon ; Dyslipidemias ; Genotype ; Humans ; Real-Time Polymerase Chain Reaction*