3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder characterized by a defect in leucine catabolism. We report the case of an 80-day-old patient with 3-methylcrotonyl-CoA carboxylase deficiency who had elevated levels of 3-hydroxyisovalerylcarnitine (45.56 micromol/L; reference range, <0.65 micromol/L), which was detected using tandem mass spectrometry during newborn screening, and elevated levels of 3-hydroxyisovaleric acid (375.75 mmol/mol Cr) and 3-methylcrotonylglycine (502.36 mmol/mol Cr ), which were detected in urine organic acid analysis. We performed direct sequence analysis of all the exons of the MCCC1 and MCCC2 genes. No mutations were detected in the direct sequence analysis of MCCC1. However sequencing of the MCCC2 gene revealed a mutation caused by a heterozygous G to C transversion [c.313G>C (p.Gly105Arg)] at nucleotide position 313 and a mutation caused by a heterozygous A to T transversion [c.1252A>T (p.lle418Phe)] at nucleotide position 1252. Identification of these 2 novel MCCC2 gene mutations in our patient suggested that analysis of the MCCC1 and MCCC2 genes might prove useful in the diagnosis of 3-methylcrotonyl-CoA carboxylase deficiency.
Carnitine ; Exons ; Glycine ; Humans ; Infant, Newborn ; Leucine ; Mass Screening ; Reference Values ; Sequence Analysis ; Tandem Mass Spectrometry ; Valerates

There have been a few reports of hemophagocytic lymphohistiocytosis (HLH) with chromosomal abnormalities. Clonal chromosomal abnormalities in HLH patients are usually found in association with hematologic malignancies and rarely with epstein-barr virus (EBV) infection. Here, we report a fatal case of HLH with clonal karyotype abnormalities. A 75-yr-old man was admitted with persistent anorexia and high fever. Laboratory data revealed pancytopenia, hypofibrinogenemia, hyperferritinemia, prolonged prothrombin time and activated partial thromboplastin time, and marked elevated level of serum transaminases. In real time-PCR using whole blood, EBV DNA was not detected but cytomegalovirus (CMV) DNA was detected. The bone marrow aspiration smear showed hyperplasia of mature histiocytes with prominent hemophagocytosis. In chromosomal analysis of bone marrow aspirates, complex chromosomal abnormalities were found. In spite of steroid pulse therapy and antibiotic treatment, he died of disseminated intravascular coagulopathy.
Anorexia ; Bone Marrow ; Chromosome Aberrations ; Cytomegalovirus ; DNA ; Fever ; Hematologic Neoplasms ; Herpesvirus 4, Human ; Histiocytes ; Humans ; Hyperplasia ; Karyotype ; Lymphohistiocytosis, Hemophagocytic ; Pancytopenia ; Partial Thromboplastin Time ; Prothrombin Time ; Transaminases

BACKGROUND: In most clinical microbiology laboratories, inoculation of specimens on plates is performed manually and is a time-consuming process. The efficiency of this process can be improved by using an automated instrument. Currently, several automated instruments have been introduced for inoculation of samples. In this study, we have evaluated an automated instrument, PREVI Isola(R) (Biomerieux, France), used for inoculation of body fluids and urine specimens. METHODS: Both manual and automated instrument methods were used to inoculate 74 body fluid and 204 urine samples. Precision was evaluated by testing 3 types of urine samples (A, 6x10(3) colony-forming units (CFU)/mL; B, 3x10(4) CFU/mL; and C, >10(6) CFU/mL) in replicates of 20. Results of the 2 methods were compared by counting the isolated colonies on agar plates after incubation. The time required for both methods was also compared. RESULTS: The coefficient of variation (CV) of samples A, B, and C examined using the automated instrument method was 176.1%, 18.1%, and 12.6%, respectively. The sensitivity and specificity of testing body fluid samples were 77% and 100%, respectively, and those of urine samples were 87% each. The time required for testing 15 body fluid specimens and that for inoculation of each specimen was 9.7 min shorter using PREVI Isola(R) than using the manual method. CONCLUSIONS: The results of body fluid and urine culture by inoculation using the automated instrument, PREVI Isola(R), showed relative good agreement with those obtained using the manual method. The use of PREVI Isola(R) would be expected to reduce the time and labor involved in inoculating various kinds of specimens.
Agar ; Automation, Laboratory ; Body Fluids ; Microbiological Techniques ; Sensitivity and Specificity ; Stem Cells

BACKGROUND: Malaria is a problematic disease in Korea, and microscopic examination of Giemsa-stained blood smear has been used as the gold standard for its diagnosis. However, this technique is time-consuming and has low sensitivity in samples with low numbers of malarial parasites (<20 parasites/microL). Here, we evaluated the performance characteristics of the LG Advansure(TM) Malaria P.f./P.v. real-time QPCR (LG life sciences, Korea). METHODS: Blood samples from 173 persons who visited Korea University Ansan Hospital were evaluated. QPCR was performed in 73 malaria patients and 100 healthy subjects by using the LG Advansure Malaria P.f./P.v. real-time QPCRR kit, and the results were compared with those of microscopy. The detection limit of this kit was determined by serial dilution of Plasmodium-infected blood with normal blood (blood not infected with Plasmodium). RESULTS: Among the 73 patients that were microscopically confirmed to have malaria (Plasmodium vivax infection, N=70, P. falciparum infection, N=3), 69 patients were diagnosed with P. vivax infection and 3 were diagnosed with P. falciparum infection by LG Advansure(TM) Malaria P.f./P.v. real-time QPCR. Both the tests indicated absence of infection in the 100 healthy subjects. The detection limit of LG Advansure(TM) Malaria P.f./P.v. real-time QPCR was 0.1 parasite/microL. CONCLUSIONS: LG Advansure(TM) Malaria P.f./P.v. real-time QPCR is a very sensitive and specific technique and can be used as a confirmatory test for malaria.
Biological Science Disciplines ; Humans ; Korea ; Limit of Detection ; Malaria ; Microscopy ; Parasites

BACKGROUND: The Coapresta 2000 (Sekisui Medical CO., LTD, Japan) is a fully automated random-access multiparameter hemostasis coagulation analyzer, which is equipped with a photo-optical clot detection unit and a cap-piercing system. It is able to perform clotting time assays as well as colorimetric assays (synthetic substrate method and latex turbidimetric method). In this study, we evaluated the analytical performance of the Coapresta 2000 for coagulation test items and compared with that of the ACL-TOP (Instrumentation Laboratory, Lexingtion, MA, USA) analyzer, which is currently used for routine coagulation test items in our hospital. METHODS: The Coapresta 2000 was evaluated with respect to its technical characteristics in the determination of 8 routine coagulation test items: prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin-degradation product (FDP) antithrombin III, D-dimer, factors VIII and IX. Analyse-it (Analyse-it Software Ltd, UK) and SigmaStat (Systat Software, Inc., USA) were used for statistical analysis between items on the Coapresta 2000 and the ACL-TOP analyzer. RESULTS: The intra-assay and inter-assay coefficients of variation (CV) were below 5% for both groups of samples having values within the reference interval and outside the reference interval. Significant interference was observed with hemolytic and icteric samples. Carryover was not detected. The results obtained by Coapresta 2000 were well correlated with those obtained by the ACL-TOP analyzer (r2 in the range from 0.781 to 0.969). CONCLUSIONS: We concluded that Coapresta 2000 analyzer was well correlated with ACL-TOP analyzer for the routine coagulation test items tested.
Antithrombin III ; Fibrin Fibrinogen Degradation Products ; Fibrinogen ; Hemostasis ; Latex ; Partial Thromboplastin Time ; Prothrombin Time

BACKGROUND: Hepcidin has recently been known as a negative regulatory hormone of iron. Hepcidin precursor, pro-hepcidin has been used as a surrogate and reported to be related to iron deficiency. We investigated serum pro-hepcidin levels in patients with iron deficiency anemia (IDA), anemia of chronic disorder (ACD) and ACD concomitant iron deficiency (ACD/ID) to assess its usefulness as a marker of iron deficiency and examined whether its level is associated with anemia, iron status or inflammation profiles involved in the synthesis of hepcidin. METHODS: We enrolled 50 patients with IDA, 46 with ACD, 12 with ACD/ID and 60 healthy controls. Complete blood cell count, iron parameters (iron, TIBC, trasferrin saturation, ferritin), C-reactive protein (CRP) and serum pro-hepcidin were measured. RESULTS: Patients with iron deficiency, the IDA group and ACD/ID group had lower serum pro-hepcidin levels than healthy controls and the ACD group. The cutoff value of pro-hepcidin for detecting iron deficiency was 230 ng/mL (sensitivity 88.1%, specificity 51.2%). Patients with increased CRP showed higher mean pro-hepcidin level than those with normal CRP and the difference was significant in the IDA group (P=0.02). And serum pro-hepcidin level was positively correlated with CRP level (r=0.30, P=0.04) in the IDA group but not with hemoglobin. CONCLUSIONS: In patients with anemia, pro-hepcidin measurement may be useful for differentiating anemia patients with iron deficiency, IDA and ACD/ID from those with ACD. Serum pro-hepcidin levels may be more affected by inflammation than by the degree of anemia.
Anemia ; Anemia, Iron-Deficiency ; Antimicrobial Cationic Peptides ; Blood Cell Count ; C-Reactive Protein ; Humans ; Inflammation ; Iron ; Protein Precursors ; Sensitivity and Specificity

BACKGROUND: The purpose of the present study was to investigate the clinico-hematological findings of bone marrow (BM) involvement and leukemic phase in Korean patients with non-Hodgkin lymphoma (NHL). METHODS: We included 791 patients with NHL that were classified with the WHO (2008) criteria. Laboratory data, bone marrow histomorphologic features and medical records were reviewed. Leukemic phase was defined as when the proportion of neoplastic lymphoid cells comprised more than 10% of leukocytes in the peripheral blood or more than 25% of nucleated cells in the BM. RESULTS: We found that 21.7% (172/791) of the patients had BM involvement, and 6.2% (49/791) developed leukemic phase of the disease. NHL subtypes showing high frequencies of leukemic phase development were mantle cell lymphoma (40%), angioimmunoblastic T cell lymphoma (40%), lymphoblastic lymphoma (36.4%), and Burkitt lymphoma (26.1%). Compared to B-cell type, T-cell type of NHL showed significantly higher frequencies of BM involvement (18.6% vs 30.9%; P=0.0004) and leukemic phase development (4.8% vs 10.3%, P=0.008). Complete remission rate was significantly lower in leukemic (55.6%) than in non-leukemic (85.9%) group of patients (P=0.0002), whereas relapse rate was not different between the two groups. Death rate was higher in leukemic (46.9%) than in non-leukemic (30.1%) group of patients, and the 5-yr overall survival probability was significantly lower in leukemic group (P=0.02). CONCLUSIONS: The incidence of leukemic phase development in NHL was lower in Korean patients than that reported for Western populations and higher in T-cell lymphoma. We confirmed that the presence of leukemic phase in NHL patients is associated with a poor prognosis.
B-Lymphocytes ; Bone Marrow ; Burkitt Lymphoma ; Humans ; Incidence ; Leukocytes ; Lymphocytes ; Lymphoma, Mantle-Cell ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell ; Medical Records ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; T-Lymphocytes

BACKGROUND: Accuracy of laboratory test results is an important issue. New guidelines for specimen delivery systems are needed for appropriate pretreatment of specimens and accuracy of results. METHODS: We evaluated various laboratory profiles, comparing the effects of specimen rack holders and coolants within transport containers. The hematology profiles (complete blood cell count [CBC], erythrocyte sedimentation rate [ESR]), chemistry profiles (aspartate aminotransaminase [AST], alanine aminotransaminase [ALT], gamma-glutamyl transferase [gamma-GT], electrolytes [Na, K, Cl], glucose, lactate dehydrogenase [LD], creatinine kinase [CK]), and coagulation profiles (prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen level). We also investigated the effects of transportation time including the presence or absence of hemolyzation. We received from 9 different university hospital laboratories using conventional transporation methods. RESULTS: Hemolytic features were seen in short drawn specimens. Fewer result variations were observed in specimens transported with coolants. Average specimen transportation time was 11.3 hours, and average temperatures of container was 10.9degrees C with coolant and 25.0degrees C without coolants. Non-centrifuged specimens transported with coolants showed increased serum K levels than centrifuged specimens. Coagulation tests showed less than a 10% differences. Centrifuged specimen prior to transportation showed no hemolyzation and no differences in results. CONCLUSIONS: Appropriate temperatures for each analyte should be defined to ensure the accuracy of results. To reduce hemolyzation, appropriate temperature and rack holder should be used. Temperature of the transport container should be monitored in objectively. Coagulation tests should be added as referral tests, if appropriate specimen transport monitoring system for time and temperature could be adopted.
Alanine ; Blood Cell Count ; Blood Sedimentation ; Creatinine ; Dietary Sucrose ; Electrolytes ; Fibrinogen ; Glucose ; Hematology ; Hemolysis ; L-Lactate Dehydrogenase ; Laboratories, Hospital ; Partial Thromboplastin Time ; Phosphotransferases ; Referral and Consultation ; Transferases ; Transportation

No abstract available.
Hemoglobins

Atypical chronic myeloid leukemia (aCML) is a rare leukemic disorder that shows myelodysplastic and myeloproliferative features simultaneously. The Janus kinase 2 gene V617F mutation (JAK2V617F) in aCML has been the source of much controversy. Some JAK2V617F positive cases have been reported but others observed no JAK2V617F mutation in aCML as defined by WHO classification. Recently, we experienced a case of aCML with JAK2V617F mutation with typical myelodysplastic/myeloproliferative features in peripheral blood and bone marrow aspirates. The karyotype was normal and no BCR/ABL1, PDGFRA or PDGFRB gene rearrangement was noted with FISH analysis. JAK2V617F mutation of the case was identified with amplification refractory mutation system PCR and direct sequencing. We also studied JAK2V617F mutation status in 3 additional cases of previously diagnosed aCML in our institution, but no mutation was identified.
Bone Marrow ; Gene Rearrangement ; Janus Kinase 2 ; Karyotype ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative ; Myelodysplastic Syndromes ; Myeloproliferative Disorders ; Polymerase Chain Reaction ; Receptor, Platelet-Derived Growth Factor beta