Thalassemia is a common public health problem among Malays. Hemoglobin C (Hb C) is a hemoglobin beta variant resulting from a single base mutation at the 6th position of the beta-globin gene leading to the substitution of glycine for glutamic acid. Hb C is commonly detected in West Africans and in African American but has not been reported in Malaysia. It can be falsely diagnosed as HbE trait in the Malaysian Thalassemia Screening Program which utilizes cellulose acetate hemoglobin electrophoresis. This is the first reported case of Hb AC heterozygote status in a Malay family, with unusual splenomegaly in one of the family members.
In the newborn the diagnosis of alpha thalassaemia trait is easier because of the presence of haemoglobin Bart's (Hb Bart's). Alpha thalassaemia is common in Southeast Asia. Malaysians are composed of the ethnic groups Malays, Chinese, Indians and Eurasians. Hb Bart's itself is not a simple inherited character but arises from genetically determined imbalance in the biosynthesis of alpha and non alpha chains. 58% of the cord blood samples tested showed raised levels of Hb Bart's. In the Chinese the most common cause of hereditary haemolytic anaemia is haemoglobin H and hydrops foetalis is seen. The rare occurrence of these syndromes in the Malays and Indians in spite of the presence of Hb Bart's indicates an altered expression of the alpha thalassaemia gene in these populations.
A survey of abnormal haemoglobins and hereditary ovalocytosis was carried out among 629 Malays of Minangkabau descent in the Ulu Jempul District of Kuala Pilah, in the state of Negri Sembilan in West Malaysia.. Several abnormal haemoglobins were found with the following frequencies: Hb E 5.25%, Hb CoSp 2.38%, Hb A2 indonesia 0.80%, a fast moving Hb with a Mobility between A and Bart's 0.64% and Hb Q 0.16%. Hereditary ovalocytosis was found in 13.2% of these people. None of the persons with hereditary ovalocytosis had any evidence of haemolysis.
OBJECTIVE AND STUDY DESIGN: A nonrandomized open labeled clinical trial to evaluate the efficacy and tolerability of Dianex (a poly herbal formulation developed by Apex Laboratories [PVT] Chennai, Tamil Nadu, India) in type 2 diabetes mellitus was carried out during a 6-month period.
SETTING/LOCATION: This study was conducted in TMA Pai Hospital, Udupi, South India.
SUBJECTS: A total of 40 patients were recruited for this study. Three patients dropped out of the study leaving a total of 37 patients (11 for monotherapy and 26 for add on therapy).
OUTCOME MEASURES: Eighteen (18) clinical variables were investigated, including liver enzymes, kidney function tests, hematologic parameters, blood glucose, and insulin and lipid profiles.
RESULTS: at the end of 12 weeks it was found that there was a significant decrease in the level of glycated hemoglobin, fasting plasma insulin level, insulin resistance, and systolic and diastolic blood pressure. At the end of 24 weeks results were similar to those at 12 weeks. Dianex did not alter the liver function tests, hematological parameters, or kidney function tests.
CONCLUSION: In this preliminary study, Dainex is found to be an effective adjuvant drug with either oral antidiabetic agents or insulin that can be used in the control of blood sugars in diabetic patients. Dianex is a safe drug that does not cause any clinical, hematological or biochemical alteration in major organ systems.
A new haemoglobin, Haemoglobin Malay is described in a 22 year old Malay. Structural analysis showed a AAC----AGC mutation in codon 17, with the production of an abnormal beta chain (beta Malay) that has an Asn----Ser substitution at position beta 19. This haemoglobin variant could not be detected by conventional procedures.
Hereditary stomatocytic ovalocytosis and haemoglobin E are two genes present in 3-5% of Malays. This is a report of a 22 year old Malay college student with homozygous haemoglobin E and hereditary stomatocytic ovalocytosis where the clinical effects seen were the result of the summation of these genes: he was asymptomatic, presenting with moderate jaundice, moderate hepatosplenomegaly, and a mild haemolytic anaemia.
Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.
Thalassaemia carriers are common in the Asian region including Malaysia. Asymptomatic patients can be undiagnosed until they present for their antenatal visits. Devastating obstetric outcome may further complicate the pregnancy if both parents are thalassaemia carriers leading to hydrophic fetus due to haemoglobin Bart's disease. However in certain cases where unexplained hydrops fetalis occur in parents with heterozygous thalassaemia carrier,mutated α genes should be suspected. We report a twenty-nine year old woman in her third pregnancy with two previous pregnancies complicated by early neonatal death at 21 and 28 weeks of gestation due to hydrops fetalis. DNA analysis revealed the patient to have heterozygous (--SEA) α-gene deletion, while her husband has a compound heterozygosity for α(3.7) deletion and codon 59 (GGC → GAC) mutation of the α-gene. This mutation, also known as hemoglobin Adana, can explain hydrops fetalis resulting from two alpha gene deletions from the patient (mother) and a single alpha gene deletion with mutation from the father. The third pregnancy resulted in a grossly normal baby boy with 3 α-gene deletions (HbH disease). We postulate that, in view of heterogenisity of the α-thalassaemia in this patient with severely unstable haemoglobin Adana chains from her husband, there will be a 25% possibility of fetal hydrops in every pregnancy.
Alpha (Α) thalassaemia is the most common inherited disorder in Malaysia. The clinical severity is dependant on the number of Α genes involved. Full blood count (FBC) and haemoglobin (Hb) analysis using either gel electrophoresis, high performance liquid chromatography (HPLC) or capillary zone electrophoresis (CE) are unable to detect definitively alpha thalassaemia carriers. Definitive diagnosis of Α-thalassaemias requires molecular analysis and methods of detecting both common deletional and non-deletional molecular abnormailities are easily performed in any laboratory involved in molecular diagnostics. We carried out a retrospective analysis of 1623 cases referred to our laboratory in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for the diagnosis of Α-thalassaemia during the period October 2001 to December 2012. We examined the frequency of different types of alpha gene abnormalities and their haematologic features. Molecular diagnosis was made using a combination of multiplex polymerase reaction (PCR) and real time PCR to detect deletional and non-deletional alpha genes relevant to southeast Asian population. Genetic analysis confirmed the diagnosis of Α-thalassaemias in 736 cases. Majority of the cases were Chinese (53.1%) followed by Malays (44.2%), and Indians (2.7%). The most common gene abnormality was ΑΑ/--(SEA) (64.0%) followed by ΑΑ/-Α(3.7) (19.8%), -Α(3.7) /--(SEA) (6.9%), ΑΑ/ΑΑCS (3.0%), --(SEA)/--(SEA) (1.2%), -Α(3.7)/-Α(3.7) (1.1%), ΑΑ/-Α(4.2) (0.7%), -Α(4.2)/--(SEA (0.7%), -Α(3.7)/-Α(4.2) (0.5%), ΑΑ(CS)/-- SEA) (0.4%), ΑΑ(CS)/ΑΑ(Cd59) (0.4%), ΑΑ(CS)/ΑΑ(CS) (0.4%), -Α(3.7)/ΑΑ(Cd59) (0.3%), ΑΑ/ΑΑ(Cd59) (0.1%), ΑΑ(Cd59)/ ΑΑ(IVS I-1) (0.1%), -Α(3.7)/ΑΑ(CS) (0.1%) and --(SEA) /ΑΑ(Cd59) (0.1%). This data indicates that the molecular abnormalities of Α-thalassaemia in the Malaysian population is heterogenous. Although Α-gene deletion is the most common cause, non-deletional Α-gene abnormalities are not uncommon and at least 3 different mutations exist. Establishment of rapid and easy molecular techniques is important for definitive diagnosis of alpha thalassaemia, an important prerequisite for genetic counselling to prevent its deleterious complications.
Haemoglobin Constant Spring (Hb CS) mutation and single gene deletions are common underlying genetic abnormalities for alpha thalassaemias. Co-inheritance of deletional and non-deletional alpha (alpha) thalassaemias may result in various thalassaemia syndromes. Concomitant co-inheritance with beta (beta) and delta (delta) gene abnormalities would result in improved clinical phenotype. We report here a 33-year-old male patient who was admitted with dengue haemorrhagic fever, with a background history of Grave's disease, incidentally noted to have mild hypochromic microcytic red cell indices. Physical examination revealed no thalassaemic features or hepatosplenomegaly. His full blood picture showed hypochromic microcytic red cells with normal haemoglobin (Hb) level. Quantitation of Hb using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) revealed raised Hb F, normal Hb A2 and Hb A levels. There was also small peak of Hb CS noted in CE. H inclusions was negative. Kleihauer test was positive with heterocellular distribution of Hb F among the red cells. DNA analysis for alpha globin gene mutations showed a single -alpha(-3.7) deletion and Hb CS mutation. These findings were suggestive of compound heterozygosity of Hb CS and a single -alpha(-3.7) deletion with a concomitant heterozygous deltabeta thalassaemia. Co-inheritance of Hb CS and a single -alpha(-3.7) deletion is expected to result at the very least in a clinical phenotype similar to that of two alpha genes deletion. However we demonstrate here a phenotypic modification of alpha thalassemia presumptively as a result of co-inheritance with deltabeta chain abnormality as suggested by the high Hb F level.
A 2-year-old Malay boy was brought to the University Malaya Medical Centre for thalassaemia screening. Physical examination revealed thalassaemia facies, pallor, mild jaundice, hepatomegaly and splenomegaly. Laboratory investigations on the patient including studies on the parents lead to a presumptive diagnosis of homozygous Haemoglobin Lepore (Hb Lepore). The aim of this paper is to increase awareness of this rare disorder, this being the first case documented in Malaysia in a Malay. The case also demonstrates the need for this disorder to be included in the differential diagnosis of patients presenting clinically like thalassemia intermedia or thalassemia major. Accurate diagnosis would provide information necessary for prenatal diagnosis, proper clinical management and genetic counseling. The clinical, haematological and laboratory features of this disorder are discussed in this paper.