Shine &amp; Lal index as a predictor for early detection of β-thalassemia carriers in a limited resource area in Bandung, Indonesia

Maskoen, Ani Melani; Reniarti, Lelani; Sahiratmadja, Edhyana; Sisca, Joice; Effendi, Sjarif Hidajat

doi:10.1186/s12881-019-0868-x

Cited by 14 publications

(15 citation statements)

References 23 publications

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“…Whereas, CD8/9 (+G) was found in a β-thalassemia carrier in Bandung. (21) These mutations lead to formation of a stop codon or called premature translation-termination codons (PTCs), resulting a very short protein. The presence of PTC can trigger the destruction mechanism of mRNA namely NMD pathway.…”

Section: Discussionmentioning

confidence: 99%

Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

et al. 2021

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BACKGROUND: β-thalassemia is an inherited blood disorder that relatively common in Southeast Asian countries. In Indonesia, it is estimated that 200,000 infants with thalassemia carrier born each year. Mutation causing β-thalassemia is highly varied and relatively specific in a population. This study aimed to identify the mutations responsible for β-thalassemia from Thalassemia Carrier Screening conducted in Yogyakarta Special Region. This information is beneficial for developing a strategic prevention program to control thalassemia in the region.METHODS: Twenty-eight blood samples of haematologically suspected β-thalassemia from participant of thalassemia screening program in Yogyakarta Special Region were investigated for β-globin gene mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS) and DNA sequencing.RESULTS: Our samples showed average HbA2 value of 5±0.81% and HbF value of 2±2.29%. It showed eight abnormal erythrocyte morphologies dominated by hypochromia (96.4%), cigar cell (85.7%), and microcytosis (78.6%). Our molecular investigation identified three splice-site mutations namely InterVening Sequence (IVS)-1-5 (G>C) (71.4%), IVS-1-2 (T>C) (7.1%), and IVS-1-1 (G>T) (3.6%), two frameshift mutations that are CD35 (-C) (10.7%) and CD8/9 (+G) (3.6%), and a missense mutation of CD6 (GAG>GTG) (3.6%).CONCLUSION: Our study concluded on a high prevalence of IVS-1-5 (G>C) mutation in Yogyakarta Special Region. This mutation information is significant for developing a strategic prevention program to control thalassemia in the region, for example for developing a rapid molecular test for future screening program.KEYWORDS: β-Globin gene, thalassemia, screening, carrier, mutation, Yogyakarta

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Section: Discussionmentioning

confidence: 99%

Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

et al. 2021

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“…[4,5] Various formulas using a complete blood count have been developed to detect β-thalassemia carriers in areas where the prevalence of thalassemia major is high; however, specificity and sensitivity vary across regions. [4,6] In an attempt to simplify the differential diagnosis between IDA and β-thalassemia minor, several indices using blood cell count parameters have been suggested. [4] According to many studies, the formula developed by Green and King {[(MCV 2 ) x RDW] / (Hb x 100)}, Sirdah et al Formula (MCV -RBC -3xHb), Matos and Carvalho Index (1.91 x RBC) + (0.44 x MCHC), and Mentzer Index (MCV/RBC) have a good performance.…”

Section: Introductionmentioning

confidence: 99%

Reliability of Different RBC Indices and Formulas in the Discrimination of ?-Thalassemia Minor and Iron Deficiency Anemia in Surabaya, Indonesia

2021

IJFMT

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In this study, we evaluated the RBC indices in differentiating β-thalassemia minor and iron deficiency anemia in a healthcare center. This was an observational analytic study with a cross-sectional design using blood specimens of children aged 3 years to 17 years with microcytic hypochromic anemia based on the results of complete blood counts and evaluation of peripheral blood smears. Calculation of the RBC indices was performed as an initial screening to differentiate β-thalassemia minor and iron deficiency anemia. Iron profile examination and hemoglobin electrophoresis were performed to confirm the diagnosis of β-thalassemia minor and iron deficiency anemia. The results of the independent samples t-test showed significant differences in Hb, MCV, MCH, and MCHC between β-thalassemia minor and iron deficiency anemia (p <0.05). The results of the Mann Whitney test showed a significant difference in the Mentzer Index to distinguish between β-thalassemia minor and iron deficiency anemia (p <0.05). Also, the results of the independent samples t-test showed significant differences in the Green & King formula, Sirdah et al. formula, and the Maltos and Carvalho Index (p <0.05). The Green and King formula has a diagnostic sensitivity of 78.6% and a specificity of 76.6% and an accuracy of 78.03%. Various formulas based on the results of complete blood count parameters have been developed to detect β-thalassemia minor in areas with a high prevalence of β-thalassemia with different sensitivity and specificity. In this study, it showed that the Green and King formula has a diagnostic sensitivity of 78.6% and a specificity of 76.6%, and an accuracy of 78.03%. Green and King's formula can be applied as an initial screening to differentiate β-thalassemia minor and iron deficiency anemia

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“…Thalassemia major becomes the fifth in the list of national catastrophic diseases, and β-thalassemia minor or trait or carrier in the western part of Indonesia is estimated around 6 to 10%. 1 However, a nationwide prevention program is not available yet. Therefore, it is challenging to detect thalassemia carriers in Indonesia, which is well known for its ethnic diversity.…”

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confidence: 99%

“…Samples with a very high HbA2 >8% were all confirmed to have G>A mutation at codon 26, known as HbE variant; therefore, Hb E carriers would have been picked up by high-performance liquid chromatography (HPLC) alone and would thus not require DNA analysis. 1 Of note, both SLI and MI did not cover HbE, leading to a possible false-negative result of some cases during screening ( Table 2 ). Interestingly, other samples with HbA2 value >3.5% were confirmed to have no mutation in common β-globin from South East Asia (SEA) region.…”

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confidence: 99%

“…The population in eastern Indonesia has a different spectrum of mutation than western Indonesia, where IVS1nt-5 mutation is prevalent. 1 These samples need to be further explored for β globin gene, including its promoter region to polyA region, using the sequencing method. Alternatively, another set for β-globin examination specific to the Mediterranean area (MEA) or the India & Middle-East area (IME) might give more information.…”

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confidence: 99%

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Thalassemia carrier detection among pregnant women

Sahiratmadja

Seu²,

Nainggolan

et al. 2020

Mediterr J Hematol Infect Dis

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Thalassemia major becomes the fifth catastrophic disease in Indonesia, however, national wide screening program is not mandatory. This study aimed to re-assess the validity of the various erythrocyte indices in determining ?-thalalssemia carrier among pregnant women in a low resource setting area. An analytic study was performed, comparing conventional cut-off various erythrocyte indices with new modified cut-offs by Kumar et al. The concordance analysis was calculated with Mentzer Index (MI) as reference. The validity of erythrocyte indices against hemoglobin (Hb) A2 were analysed, confirmed by molecular examination for ?- and common ?-Globin South East Asia population. Of 102 pregnant women, 34% was still anemic after completion of 90 iron pills. The concordance of conventional cut-off Shine & Lal index (<1530) was none to slight in agreement (kappa 0.097) to conventional cut-off MI (<13). The concordance of SLI increased significantly to substantial agreement when both used modified cut-offs (kappa 0.729). However, both SLI and MI had missed most of HbE carriers and ?-thalassemia carriers which seemed to be prevalent in this population as shown by DNA examination. In contrary, simple MCV<80fl and MCH<27pg had covered those carriers. This is the first study from Nusa Tenggara Timur, a low resource area in Indonesia in attempt to mass screen thalassemia carriers in this area where a simple MCV<80 fL and MCH<27pg have been used for preliminary screening rather than other indices. Since the population in eastern part of Indonesia has different genetic background compared to the west, DNA analysis is of great interest to map the spectrum of globin mutations.

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Shine & Lal index as a predictor for early detection of β-thalassemia carriers in a limited resource area in Bandung, Indonesia

Cited by 14 publications

References 23 publications

Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

Reliability of Different RBC Indices and Formulas in the Discrimination of ?-Thalassemia Minor and Iron Deficiency Anemia in Surabaya, Indonesia

Thalassemia carrier detection among pregnant women

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