The Xpert® MTB/RIF assay evaluation in South Korea, a country with an intermediate tuberculosis burden.

SETTING: A central hospital laboratory in South Korea. OBJECTIVE: To evaluate the usefulness of the Xpert® MTB/RIF assay in a country with an intermediate tuberculosis burden. DESIGN: A total of 71 real-time polymerase chain reaction-positive sputum sediments were tested within 24 h by the Xpert MTB/RIF assay. Mycobacterium tuberculosis detection was compared with smear microscopy and culture. Rifampicin (RMP) resistance was compared with a culture-based method and rpoB gene sequencing. We also assessed the limit of detection for mutant proportions and time savings in diagnosis. RESULTS: The Xpert MTB/RIF assay detected M. tuberculosis in 71 (100%) specimens (32 smear-positive, 39 smear-negative). This assay showed 100% (62/62) concordance with drug resistance confirmed by culture and 98.4% (61/62) concordance with sequencing. A specimen containing approximately 50% of mutant p.His526Tyr was falsely interpreted as wild-type bacilli by this assay. The minimal detection ratio was 5:1 of mutant vs. wild-type cells. The median time saved was 18.5 days (range 9-30) for the diagnosis of M. tuberculosis and 81.5 days (65-136) for RMP susceptibility in smear-negative, culture-positive patients. CONCLUSIONS: The Xpert MTB/RIF assay showed high sensitivity in detecting M. tuberculosis with information on RMP resistance, and had a more rapid time to diagnosis compared to conventional tests; however, the location and amount of mutation may affect test sensitivity.

A Korean family with a dominantly inherited beta-thalassemia due to Hb Durham-N.C./Brescia.

We describe the molecular and the hematological characteristics of a Korean family with a dominantly inherited beta-thalassemia. Carriers were characterized by moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F levels, and splenomegaly. DNA analysis revealed a CTG (Leu) to CCG (Pro) substitution at codon 114 of the beta-globin gene, that leads to a highly unstable hemoglobin variant, Hb Durham-N.C./Brescia, and this was linked to the beta haplotype V, [+----+-], and framework 2. RNA analysis showed that the proband had comparable levels of mutant and normal beta-mRNA. Translation of the mutant mRNA would give rise to non-functional hyperunstable beta-globin chains, and their degradation would, by placing an additional burden on the proteolytic process of the red blood cell precursors, result in a more severe phenotype.

Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7.

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. CAG repeat expansions in the causative genes have been identified as the basic cause of several types of SCAs, and have been used for the diagnoses and classifications of patients with ataxia. In order to assess the frequency and CAG repeat size ranges of SCAs, and to establish an effective strategy for molecular diagnosis, we performed a molecular analysis of SCA1, SCA2, SCA3, SCA6, and SCA7 in 76 patients. These patients were as follows: 32 with dominant inheritance, 39 sporadic cases, and 5 with unknown family histories. The normal and affected CAG repeat size ranges were established at five SCA loci in Koreans, which was consistent with previous reports. The total prevalence of the five types of SCAs was 39.5% in the 76 patients with ataxia, regardless of their family history. It was 75.0% in the 32 families with a dominant inheritance. The most frequent type was SCA3 (15.8%), followed by SCA2 (14.5%). Both types combined formed 76.7% of the 30 patients with CAG expansions. SCA1, SCA6, and SCA7 were less frequent, affecting 3.9%, 2.6%, and 2.6% of the cases, respectively. This mutation spectrum is quite different from a previous report concerning Koreans, but is similar to the distributions that are seen in several ethnic populations worldwide. For a correct and effective diagnosis of SCAs, we suggest that a molecular diagnosis be undertaken, even in patients without a family history, as well as those with a family history. A stepwise approach is also recommended. Patients with ataxia should be tested for SCA2 and SCA3. Individuals testing negative should be tested for SCA1, SCA6, and SCA7.

Spinocerebellar ataxia type 2 in seven Korean families: CAG trinucleotide expansion and clinical characteristics.

Studies on spinocerebellar ataxias (SCA) have been hampered by a lack of disease markers. Clinical and pathological heterogeneity also made the classification unreliable. Linkage studies established that there are multiple subtypes of SCA. Five types are found to have unstable CAG expansion; the diagnosis can be established by molecular genetic study. Therefore, we systemically screened degenerative ataxia patients for these five SCA types, and identified eight patients with SCA2 (seven from six families and one sporadic case). This paper presents the clinical information on the seven patients, whose clinical information was available in detail. CAG repeat expansion in the patients ranged from 38 to 47 (normal control, 19 to 27). The onset ages ranged from 16 to 41 with 27.1 years as the mean, which correlated inversely with repeat lengths. All patients presented dysarthria and gait ataxia. Upper limb dysmetria or dysdiadochokinesia appeared later but progressed, causing severe disability. Slow saccade (4 patients in 7) and decreased DTR (4 in 7) were common. MRIs showed severe atrophy of the brainstem and cerebellum in all patients. We conclude that SCA2 is the most frequent type in Korea and carries rather pure cerebellar syndrome, slow saccade, and hyporeflexia.

Importance of rotavirus and adenovirus types 40 and 41 in acute gastroenteritis in Korean children.

To examine the role of rotavirus (Rv) and adenovirus types 40 and 41 (Ad40/41) in Korean children with acute gastroenteritis, we evaluated 345 children with acute gastroenteritis and 90 children without acute gastroenteritis in Seoul, Korea, during a 29-month period. Stools were tested for group A Rv antigen and for Ad40/41 by using monoclonal antibody (MAb)-based assays. Rv was found in 68% of the ill children and 19% of the controls (P less than 0.001), whereas Ad40/41 was detected in 9% of the ill children and 2% of the controls (P less than 0.05). Also, 6% of the ill children and 0.01% of the controls excreted Rv and Ad40/41 simultaneously. Among the ill children, 96% of children with Rv and 94% of those with Ad40/41 were younger than 24 months. Although a peak of Rv infection was detected in early winter in both years of the study, there was no apparent seasonal trend with Ad40/41. Diarrhea with more than 10 stools per day, vomiting, or fever was most strongly associated with Rv shedding, whereas the first two manifestations were associated with coinfection of Rv and Ad40/41. To investigate the genetic and serotypic diversity of Rv strains, we tested 195 and 144 fecal Rv specimens isolated from the gastroenteritis cases, respectively, by polyacrylamide gel electrophoresis of the segmented RNA genome and by an enzyme-linked immunosorbent assay with serotype-specific MAbs. Of the 195 specimens, 154 yielded RNA patterns characteristic of group A Rv: 18% had short electrophoretic migration patterns, 81% had long patterns, and 1% had a mixture of short and long patterns. Of the 144 specimens, serotype specificity was determined in 51%: 89% were serotype 1, 10% were serotype 2, and 1% were serotype 3. Analysis of the specimens for which electropherotypes and serotypes were available indicated that a given RNA pattern corresponded to a particular serotype, except in one strain that showed short patterns but serotype 1. We suggest that Rv and Ad40/41 in stools be accepted critically as an important cause of diarrhea among young children in Korea.

[Development of a risk factor assessment chart for screening high-risk pregnancy for use by health workers at the grass roots level].

PIP: The aim of this study is to develop a sequential examination procedure to be used by low-level health-care practitioners in the identification of high-risk pregnancies in the Republic of Korea. Data collected in 1981 from 3,838 pregnant women are used to determine the significance to birth outcomes of 48 variables selected for consideration. The 26 variables shown to have a high correlation with undesirable outcomes are then included on an examination chart. (summary in ENG)^ieng