Selamah Ghazali

Poor correlation between hemolysis and jaundice in glucose 6‐phosphate dehydrogenase‐deficient babies

Abstract Background : The role of hemolysis in the pathophysiology of neonatal jaundice (NNJ) in patients with glucose 6‐phosphate dehydrogenase (G6PD) deficiency has been questioned recently. The aim of the present study was to determine the contribution of hemolysis to the pathophysiology of jaundice in Malay neonates with G6PD deficiency and NNJ.

Factor V Leiden and Prothrombin G20210A Mutations Among Healthy Indians in Malaysia

Background: Factor V Leiden (FVL) (G1691A) and prothrombin gene (G20210A) mutations are the 2 most common inherited forms of thrombophilia. The prevalence of these 2 mutations is known to show a distinct world distribution and is most prevalent among Caucasians. Previous studies report that these mutations are rare among other populations including Malays and Chinese. The aim of this study was to determine the frequency of FVL and prothrombin gene mutations among healthy Indians in Malaysia without a family history of venous thrombosis. Materials and Methods: DNA from 71 apparently healthy Indians was analyzed for the detection of FVL and prothrombin gene mutations, using PCR-RFLP with MnlI and allele-specific PCR respectively. Results: Out of the 71 samples analyzed, 4 were heterozygous (5.6%) for FVL mutation while no homozygous FVL mutation was detected. Prothrombin gene mutation was totally absent among our subjects. Conclusion: Factor V Leiden mutation in this region probably gives different clinical outcomes, suggesting the need for future studies on FVL and environmental interactions.

The absence of factor V Leiden mutation in Malays with recurrent spontaneous abortions

The objectives of this study were to investigate the prevalence of factor V Leiden mutation in Malay women with recurrent spontaneous abortion and to clarify the contribution of the factor V Leiden mutation to recurrent miscarriages in these women.

Molecular Heterogeneity of Glucose-6-Phosphate Dehydrogenase Deficiency in Malays in Malaysia

Multiplex polymerase chain reaction (PCR) using multiple tandem forward primers and a common reverse primer (MPTP) was recently established as a comprehensive screening method for mutations in X-linked recessive diseases. In the work reported here, MPTP was used to scan for mutations of the glucose-6-phosphate dehydrogenase (G6PD) gene. Mutations in exons 3, 4, 5, 6, 7, 9, 11, and 12 of the G6PD gene were screened by MPTP in 93 unrelated Malaysian patients with G6PD deficiency. Of the 93 patients, 80 (86%) had identified mutations.Although all of these were missense mutations, identified nucleotide changes were heterogeneous, with 9 mutations involving various parts of the exons. These 9 mutations were G-to-A nucleotide changes at nucleotide 871 of the G6PD gene (G871A), corresponding to G6PD Viangchan, G6PD Mediterranean (C563T), G6PD Vanua Lava (T383C), G6PD Coimbra (C592T), G6PD Kaiping (G1388A), G6PD Orissa (C131G), G6PD Mahidol (G487A), G6PD Canton (G1376T), and G6PD Chatham (G1003A). Our results document heterogeneous mutations of the G6PD gene in the Malaysian population.

The Value of Red Blood Cells (Rbc) Indices and Osmotic Fragility Test as Screening Tests in Malay Pregnant Women with Alpha Thalassaemia

Red blood cell (RBC) parameters obtained from hematology analyser has been very useful as the first line screening for thalassaemia. The changes are prominent in most type of β-thalassaemia but milder in α-thalassaemia. RBC parameters could have been normalized especially during pregnancy and in such situation screening these patients would require a different protocol. Blood samples from two hundred (200) Malay pregnant women attended obstetric clinic at Hospital Universiti Sains Malaysia (HUSM) were collected to screen for double α-gene deletion (-SEA, and –THAI), and the two single α-globin gene deletion (–α3.7 and -α4.2). Standard hematological analyses including red blood cell count and indices, and hemoglobin quantitation were performed on the blood samples. Of these, sixteen were excluded as they had HbA2 levels more than 4% and were diagnosed as HbE or β-thalassaemia trait. Then, multiplex GAP polymerase chain reaction (PCR) analyses of α-globin gene were performed on the remaining 184 blood samples. Total of 17 from 184 subjects confirmed to have α-thalassaemia (-α3.7/αα and --SEA/ αα genotype). The RBC indices were compared between those with α-thalassaemia and normal pregnant women and they were significantly different. -α3.7 kb single gene deletion (8.1%) was the commonest type followed by double gene South East Asia (--SEA) deletion (1.1%). We conclude that mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) with the cut off value of less than 86.3fl and 27.4 pg respectively are two useful RBC indices which can be used for screening of α-thalassaemia in pregnant women.

FLT3 Gene Mutation in Childhood Acute Leukemia: A Preliminary Study

Introduction. FLT3 is a tyrosine kinase receptor involved in the proliferation and differentiation of hematopoietic stem cells. There are two types of common FLT3 gene mutation, internal tandem duplication and the D835 mutation, which are known to be associated with a poor clinical outcome in acute leukemia patients. Methods. This study evaluates the incidence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 38 pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in Hospital Universiti Sains Malaysia. DNA extraction was done from archive bone marrow samples to determine FLT3-ITD mutations using polymerase chain reaction. Results. In this pediatric series, the age ranges were 2–14 years. However, no FLT3-ITD mutations were detected in any of the samples. Conclusion. This preliminary study suggested that the incidence of FLT3 gene mutation most probably was very low in pediatrics patients diagnosed with acute leukemia. A further study with larger number of patient samples is necessary to confirm the findings and to further appreciate the prognostic value of FLT3-ITD mutation among pediatrics patients.