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α-thalassemia-associated hydrops fetalis: A rare cause of thyrotoxic cardiomyopathy

Tumian NR, Wong M, Wong CL

J Obstet Gynaecol Res, 2015 Jun;41(6):967-70.
PMID: 25510540 DOI: 10.1111/jog.12648

α°-thalassemia is a well-known cause of hydrops fetalis in South-East Asia and can be detected in utero. We report a very rare case of thyrotoxic cardiomyopathy associated with hyperplacentosis secondary to α°-thalassemia-associated hydrops fetalis. A 22-year-old primigravida with microcytic anemia presented at 27 weeks' gestation with pre-eclampsia, hyperthyroidism and cardiac failure. Serum β-human chorionic gonadotrophin was markedly elevated and abdominal ultrasound revealed severe hydropic features and enlarged placenta. Serum β-human chorionic gonadotrophin, cardiac function and thyroid function tests normalized after she delivered a macerated stillbirth. Histopathology of the placenta showed hyperplacentosis. Blood DNA analysis revealed that both patient and husband have the α°-thalassemia trait. This case illustrates a very atypical presentation of α°-thalassemia-associated hydrops fetalis and the importance of early prenatal diagnosis of α-thalassemia in women of relevant ethnic origin with microcytic anemia so that appropriate genetic counseling can be provided to reduce maternal morbidity and the incidence of hydrops fetalis.

Matched MeSH terms: alpha-Thalassemia
Heterogeneity in alpha-thalassemia interactions in Malays, Chinese and Indians in Malaysia

Wee YC, Tan KL, Chow TW, Yap SF, Tan JA

J Obstet Gynaecol Res, 2005 Dec;31(6):540-6.
PMID: 16343256 DOI: 10.1111/j.1447-0756.2005.00333.x

AIM: Interactions between different determinants of alpha-thalassemia raises considerable problems, particularly during pregnancies where antenatal diagnosis is necessary. This study aims to determine the different types of deletional alpha-thalassemia and Hemoglobin Constant Spring (HbCS), and their frequency in Malays, Chinese and Indians in Malaysia.
METHODS: DNA from 650 pregnant women from the Antenatal Clinic of the University of Malaya Medical Center in Kuala Lumpur, Malaysia who showed mean cell volume < or =89 fL and/or mean cell hemoglobin < or =28 pg were analyzed for the double alpha-globin gene South-East Asian deletion (--SEA), the -alpha3.7 and -alpha4.2 single alpha-globin gene deletions and HbCS.
RESULTS: One hundred and three (15.8%) of the pregnant women were confirmed as alpha-thalassemia carriers: 25 (3.8%) were alpha-thalassemia-1 carriers with the --SEA/alphaalpha genotype, 64 (9.8%) were heterozygous for the -alpha3.7 rightward deletion (-alpha3.7/alphaalpha), four (0.6%) were heterozygous for the -alpha4.2 leftward deletion (-alpha4.2/alphaalpha), nine (1.4%) were heterozygous for HbCS (alphaCSalpha/alphaalpha) and one (0.2%) was compound heterozygous with the -alpha3.7/alphaCSalpha genotype. The double alpha-globin gene --SEA deletion was significantly higher in the Chinese (15%) compared to the Malays (2.5%) and not detected in the Indians studied. The -alpha3.7 deletion was distributed equally in the three races. HbCS and -alpha4.2 was observed only in the Malays.
CONCLUSION: The data obtained gives a better understanding of the interactions of the different alpha-thalassemia determinants in the different ethnic groups, thus enabling more rapid and specific confirmation of alpha-thalassemia in affected pregnancies where antenatal diagnosis is necessary.
Study site: Antenatal clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: alpha-Thalassemia/complications*; alpha-Thalassemia/diagnosis; alpha-Thalassemia/genetics*; alpha-Thalassemia/prevention & control
Genetic problems and genetic services in Malaysia: a country report

Hassan K

Southeast Asian J. Trop. Med. Public Health, 1995;26 Suppl 1:11-5.
PMID: 8629087
Matched MeSH terms: alpha-Thalassemia/epidemiology*
β-Thalassemias

Thong MK, Ngim CF

N Engl J Med, 2021 Jun 03;384(22):2165.
PMID: 34077655 DOI: 10.1056/NEJMc2105064
Matched MeSH terms: alpha-Thalassemia*
Fulltext Distribution of alpha thalassaemia in 16 year old Malaysian Students in Penang, Melaka and Sabah

Rahimah AN, Nisha S, Safiah B, Roshida H, Punithawathy Y, Nurul H, et al.

Med J Malaysia, 2012 Dec;67(6):565-70.
PMID: 23770946 MyJurnal

OBJECTIVES: Alpha thalassaemia is wide spread in Malaysia and is a public health problem. This study aimed to describe the carrier frequencies of α‒thalassaemia and its distribution among major ethnic groups in three states of Malaysia.

METHODS: Educational forums were organised and study was explained to students from three schools. Students were invited to take part in the screening with parent consent. A total of 8420 adolescent students aged 16 years volunteered to participate in the study. Peripheral blood samples were analysed for complete blood counts, haemoglobin quantification and typing, and serum ferritin levels. Genomic DNA was used for screening alpha thalassaemia alleles by PCR based molecular methods.

RESULTS: We identified seven α‒globin gene defects in 341 (4.08%) students: amongst them α(+)‒ and α(0)‒thalassaemias were detected in 232 (2.77%) and 107 (1.28%) students respectively. Genotype ‒α(3.7)/αα was the most prevalent among sub-populations of Malay, indigenous communities of Sahab and Indian, while ‒‒(SEA)/αα deletion is more prevalent in Malaysian Chinese. It is estimated that 63 pregnancies annually are at risk of Hb Bart's hydrops fetalis.

CONCLUSIONS: We have demonstrated the prevalence and mutation patterns of α‒thalassaemia in the 16 year olds in three states of Malaysia. High α(0)‒thalassaemia deletions amongst the study subjects place these carriers at an increased risk of conceiving fetuses with HbH disease and Hb Bart's hydrops fetalis should they choose another heterozygous partner. It is therefore highly recommended to institute community screening programmes and provide prospective carriers with genetic counselling to help them make informed choices.

Matched MeSH terms: alpha-Thalassemia*
Fulltext A rare case of alpha-thalassaemia intermedia in a Malay patient double heterozygous for alpha(+)-thalassaemia and a mutation in alpha1 globin gene CD59 (GGC --> GAC)

George E, Jama T, Azian AS, Rahimah A, Zubaidah Z

Med J Malaysia, 2009 Dec;64(4):321-2.
PMID: 20954559

A rare case of thalassaemia-intermedia involving a non-deletion alpha thalassemia point mutation in the alpha1-globin gene CD59 (GGC --> GAC) and a deletion alpha+ (-alpha(3.7)) thalassaemia in which use of high performance liquid chromatography (HPLC) C-gram Hb subtype profile and DNA molecular analysis helped establish the diagnosis.

Matched MeSH terms: alpha-Thalassemia/genetics*
Fulltext Screening of concurrent alpha-thalassaemia 1 in beta-thalassaemia carriers

Chong YM, Tan JA, Zubaidah Z, Rahimah A, Kuldip K, George E

Med J Malaysia, 2006 Jun;61(2):217-20.
PMID: 16898315

Thalassaemia is an inherited blood disorder and is a significant public health problem in Malaysia, with many not knowing they carry the gene for thalassaemia. The two major forms are alpha and beta thalassaemia. An individual can co-inherit both the alpha and beta thalassaemia genes. This study determined the frequency of concurrent carriers of alpha thalassaemia in 231 beta thalassaemia carriers. Gap-PCR was done on extracted DNA of the beta thalassaemia samples to check for alpha thalassaemia 1 molecular defect. Eight (3.5%) samples were found to have concurrently inherited the alpha thalassaemia 1 (- -SEA) deletion. The significant carrier rate for alpha thalassaemia 1 indicates the need for the implementation of DNA analysis to complement thalassaemia screening in high risk populations.

Matched MeSH terms: alpha-Thalassemia/complications; alpha-Thalassemia/genetics; alpha-Thalassemia/epidemiology*
Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall

Alauddin H, Mohamad Nasir S, Ahadon M, Raja Sabudin RZ, Ithnin A, Hussin NH, et al.

Malays J Pathol, 2015 Dec;37(3):287-92.
PMID: 26712677

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.

Matched MeSH terms: alpha-Thalassemia/blood; alpha-Thalassemia/genetics*
Fulltext α-Thalassemia with Haemoglobin Adana mutation: prenatal diagnosis

Zainal NZ, Alauddin H, Ahmad S, Hussin NH

Malays J Pathol, 2014 Dec;36(3):207-11.
PMID: 25500521

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.

Matched MeSH terms: alpha-Thalassemia/diagnosis; alpha-Thalassemia/genetics*
Fulltext Molecular characteristic of alpha thalassaemia among patients diagnosed in UKM Medical Centre

Azma RZ, Ainoon O, Hafiza A, Azlin I, Noor Farisah AR, Nor Hidayati S, et al.

Malays J Pathol, 2014 Apr;36(1):27-32.
PMID: 24763232 MyJurnal

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.

Matched MeSH terms: alpha-Thalassemia/diagnosis; alpha-Thalassemia/ethnology*; alpha-Thalassemia/genetics*
Siriraj I Gγ(Aγδβ)0-thalassaemia causing severe thalassaemia intermedia in compound heterozygous state with IVS1-1(G→T) mutation

Wong YY, Alauddin H, Raja Sabudin RZA, Ithnin A, Jalil N, Abdul Latiff Z, et al.

Malays J Pathol, 2021 Apr;43(1):95-100.
PMID: 33903312

The Siriraj I Gγ(Aγδβ)0-thalassaemia is a novel mutation involving a 118kb deletion of the β-globin gene cluster. It was first reported in 2012 in two unrelated families from the southern part of Thailand. The carriers in the heterozygous state are clinically asymptomatic. Nonetheless, its complex interaction with other β-thalassaemia could give rise to different clinical phenotypes, ranging from mild thalassaemia intermedia to thalassaemia major. We report here a case of a six-year-old Malay boy, presented with pallor, growth failure and hepatosplenomegaly. His haemoglobin at presentation was 9.2g/dL with a mean cell haemoglobin of 22.6pg and a mean cell volume of 69.9fl. His peripheral blood smear showed features of thalassaemia intermedia. Haemoglobin (Hb) analysis revealed markedly raised Hb F (83%), normal HbA2 levels and absent HbA. Deoxyribonucleic acid (DNA) analysis showed compound heterozygous IVS1-1 (G→T) β-globin gene mutation and Siriraj I Gγ(Aγδβ)0-deletion (genotype βIVS1-1/ β Siriraj I deletion). Both his father and elder sister are carriers of Siriraj I Gγ(Aγδβ)0-thalassaemia while his mother carries IVS1-1 (G→T) gene mutation. Clinically, the patient is transfusion dependent on six weekly regime. To the best of our knowledge, this is the first reported case in Malaysia involving unique Siriraj I Gγ(Aγδβ)0-thalassaemia and IVS1-1 (G→T) in a compound heterozygous state. In summary, detection of Siriraj I Gγ(Aγδβ)0-thalassaemia is essential as this deletion can lead to severe disease upon interaction with a β-thalassemia point mutation as demonstrated in our case. The establishment of effective carrier screening and genetic counselling is important to prevent its adverse consequences.

Matched MeSH terms: alpha-Thalassemia
Haemoglobin Constant Spring (HbA2: c.427T>C) and Haemoglobin Adana (HbA2: c.179G>A) in jaundiced Malaysian term neonates with clinically significant hyperbilirubinemia

Shwe S, Boo NY, Ong HK, Chee SC, Maslina M, Ling MMM, et al.

Malays J Pathol, 2020 Aug;42(2):253-257.
PMID: 32860378

INTRODUCTION: Haemoglobin Constant Spring (Hb CoSp) and Haemoglobin Adana (Hb Adana), are two non-deletion type of α-thalassemia reported in Malaysia. Owing to their structural instability, they cause hemolysis and hyperbilirubinemia. This observational study was part of a large study investigating multiple factors associated with severe neonatal jaundice. In this part we aimed to determine the prevalence of Hb CoSp and Hb Adana and their association with clinically significant neonatal hyperbilirubinemia (SigNH, total serum bilirubin (TSB>290µmol/L)) among jaundiced Malaysian term neonates.
MATERIALS AND METHODS: The inclusion criteria were normal term-gestation neonates admitted consecutively for phototherapy. PCR-restriction fragment length polymorphism method was applied on DNA extracted from dry blood spot specimens of each neonate to detect for Hb CoSp and Hb Adana gene. Positive samples were verified by gene sequencing.
RESULTS: Of the 1121 neonates recruited (719 SigNH and 402 no-SigNH), heterozygous Hb CoSp gene was detected in only two (0.27%) neonates. Both were SigNH neonates (0.3% or 2/719). No neonate had Hb Adana variant.
CONCLUSION: Hb CoSp was not common but could be a risk factor associated with SigNH. No Hb Adana was detected.

Matched MeSH terms: alpha-Thalassemia/diagnosis*
Microcytic to hypochromic ratio as a discriminant index of thalassaemia trait in subjects with hypochromic anaemia

Wee SY, Muhamed Said SS, Raja Sabudin RZA, Alauddin H, Ithnin A

Malays J Pathol, 2020 Aug;42(2):195-201.
PMID: 32860371

INTRODUCTION: Differentiating between thalassaemia and iron deficiency anaemia (IDA) in hypochromic anaemia is a challenge to pathologists as it influences the choice of subsequent specialized confirmatory tests. In this study, we aimed to evaluate the performance of microcytic to hypochromic ratio (MicroR/ Hypo-He, M/H ratio) as a discriminant index in hypochromic anaemia.
MATERIALS AND METHODS: A retrospective study was carried out on 318 subjects with hypochromic anaemia, which comprised 162 IDA and 156 thalassaemia trait subjects with α-thalassemia, β-thalassemia and HbE trait. Optimal cut-off value, sensitivity and specificity of M/H ratio for thalassaemia trait discrimination was determined using Receiver Operating Characteristic (ROC) analysis.
RESULTS: Subjects with thalassaemia trait showed higher MicroR compared to IDA ( p< 0.001) while subjects with IDA demonstrated higher Hypo-He than thalassaemia trait (p < 0.001). M/H ratio was significantly higher in thalassaemia trait compared to IDA, with medians of 3.77 (interquartile range: 2.57 - 6.52) and 1.73 (interquartile range: 1.27 - 2.38), respectively (p < 0.001). M/H ratio ≥ 2.25 was the optimal cut-off value for discriminating thalassaemia trait from IDA in hypochromic anaemia, with the area under ROC curve (AUC) of 0.83, sensitivity of 80.8% and specificity of 71.6%.
CONCLUSIONS: M/H ratio is a useful discriminant index to distinguish thalassaemia trait from IDA in hypochromic anaemia prior to diagnostic analysis for thalassaemia confirmation. High M/H ratio is suggestive of thalassaemia trait than of IDA. However, more studies are required to establish the role of M/H ratio as a screening tool for thalassaemia discrimination in hypochromic anaemia.

Matched MeSH terms: alpha-Thalassemia/diagnosis; alpha-Thalassemia/pathology
Fulltext Detection of α-thalassaemia in neonates on cord blood and dried blood spot samples by capillary electrophoresis

Alauddin H, Langa M, Mohd Yusoff M, Raja Sabudin RZA, Ithnin A, Abdul Razak NF, et al.

Malays J Pathol, 2017 Apr;39(1):17-23.
PMID: 28413201 MyJurnal

INTRODUCTION: Haemoglobin Bart's (Hb Bart's) level is associated with α-thalassaemia traits in neonates, enabling early diagnosis of α-thalassaemia. The study aimed to detect and quantify the Hb Bart's using Cord Blood (CB) and CE Neonat Fast Hb (NF) progammes on fresh and dried blood spot (DBS) specimen respectively by capillary electrophoresis (CE).

METHODS: Capillarys Hemoglobin (E) Kit (for CB) and Capillarys Neonat Hb Kit (for NF) were used to detect and quantify Hb Bart's by CE in fresh cord blood and dried blood spot (DBS) specimens respectively. High performance liquid chromatography (HPLC) using the β-Thal Short Programme was also performed concurrently with CE analysis. Confirmation was obtained by multiplex ARMS Gap PCR.

RESULTS: This study was performed on 600 neonates. 32/600 (5.3%) samples showed presence of Hb Bart's peak using the NF programme while 33/600 (5.5%) were positive with CB programme and HPLC methods. The range of Hb Bart's using NF programme and CB programme were (0.5-4.1%) and (0.5-7.1%), respectively. Molecular analysis confirmed all positive samples possessed α-thalassaemia genetic mutations, with 23/33 cases being αα/--SEA, four -α3.7/-α3.7, two αα/-α3.7 and three αα/ααCS. Fifty Hb Bart's negative samples were randomly tested for α-genotypes, three were also found to be positive for α-globin gene mutations. Thus, resulting in sensitivity of 91.7% and 88.9% and specificity of 100% for the Capillarys Cord Blood programme and Capillarys Neonat Fast programme respectively.

CONCLUSION: Both CE programmes using fresh or dried cord blood were useful as a screening tool for α-thalassaemia in newborns. All methods show the same specificity (100%) with variable, but acceptable sensitivities in the detection of Hb Bart.

Matched MeSH terms: alpha-Thalassemia/diagnosis*
Fulltext Molecular characterisation of Haemoglobin Constant Spring and Haemoglobin Quong Sze with a Combine-Amplification Refractory Mutation System

Wee YC, Tan KL, Chua KH, George E, Tan JA

Malays J Med Sci, 2009 Jul;16(3):21-8.
PMID: 22589661 MyJurnal

BACKGROUND: The interaction of the non-deletional α(+)-thalassaemia mutations Haemoglobin Constant Spring and Haemoglobin Quong Sze with the Southeast Asian double α-globin gene deletion results in non-deletional Haemoglobin H disease. Accurate detection of non-deletional Haemoglobin H disease, which is associated with severe phenotypes, is necessary as these mutations have been confirmed in the Malaysian population.
METHODS: DNA from two families with Haemoglobin H disease was extracted from EDTA-anticoagulated whole blood and subjected to molecular analysis for α-thalassaemia. A duplex polymerase chain reaction was used to detect the Southeast Asian α-globin gene deletion. Polymerase chain reaction-restriction fragment length polymorphism analysis was then carried out to determine the presence of Haemoglobin Constant Spring and Haemoglobin Quong Sze. A combine-amplification refractory mutation system protocol was optimised and implemented for the rapid and specific molecular characterisation of Haemoglobin Constant Spring and Haemoglobin Quong Sze in a single polymerase chain reaction.
RESULTS AND CONCLUSIONS: The combine-amplification refractory mutation system for Haemoglobin Constant Spring and Haemoglobin Quong Sze, together with the duplex polymerase chain reaction, provides accurate pre- and postnatal diagnosis of non-deletional Haemoglobin H disease and allows detailed genotype analyses using minimal quantities of DNA.
KEYWORDS: Combine-ARMS; Hb Constant Spring; Hb Quong Sze; medical sciences

Matched MeSH terms: alpha-Thalassemia*
Fulltext Prenatal diagnosis of Hb Bart's hydrops fetalis in West Malaysia: the identification of the alpha thal 1 defect by PCR based strategies

George E, Mokhtar AB, Azman ZA, Hasnida K, Saripah S, Hwang CM

Singapore Med J, 1996 Oct;37(5):501-4.
PMID: 9046203

Haemoglobin Bart's hydrops fetalis is the result of complete absence of functional alpha-globin genes where the fetus is homozygous for the alpha 0-thal gene. Prenatal diagnosis can be made by analysis of fetal DNA from chorionic villus, amniotic cells and fetal blood. Earlier studies for analysing genomic DNA needed digestion with restriction enzymes and hybridisation to radiolabelled probes which took 2 weeks. We have used the polymerase chain reaction (PCR) and non-radioactive primers to identify specific target sequences with results available within 1-3 days for the diagnosis of haemoglobin Bart's syndrome. With fetal blood samples, complete absence of alpha-chain synthesis is confirmed by globin chain electrophoresis on cellulose acetate pH 6.0.

Matched MeSH terms: alpha-Thalassemia/diagnosis; alpha-Thalassemia/immunology
Fulltext Peripheral haemolysis, lipid peroxidation, iron status, and vitamin E in haemoglobin H syndromes in West Malaysia

George E, Wong HB, Jamaluddin M, Huisman TH

Singapore Med J, 1993 Jun;34(3):241-4.
PMID: 8266182

Following complete DNA characterisation patients with Hb H disease were assigned into two groups: deletional (alpha +/alpha o) and non deletional (HbCS/alpha o). Earlier studies have indicated that the group with (HbCS/alpha o) has more severe clinical problems. The serum malonyldialdehyde (MDA) levels, a secondary product of lipid peroxidation were within the normal range, though significantly higher levels of MDA were seen in the non-deletional type of Hb H disease when compared with the deletional type. Markedly low vitamin E levels were also seen in the former group. There were no significant differences in clinical severity may be attributed to an interplay of the accelerated destruction of damaged mature red blood cells secondary to the oxidative denaturation of Hb H and inclusion precipitation; higher levels of Hb H and more inclusion precipitation were seen in the group with (HbCS/alpha o). Low levels of vitamin E in the (HbCS/alpha o) group being due to its consumption in the neutralisation of free radicals formed with the oxidation of globin chains.

Matched MeSH terms: alpha-Thalassemia/blood*; alpha-Thalassemia/drug therapy; alpha-Thalassemia/genetics*
Fulltext A novel gap-PCR with high resolution melting analysis for the detection of α-thalassaemia Southeast Asian and Filipino β°-thalassaemia deletion

Kho SL, Chua KH, George E, Tan JA

Sci Rep, 2015;5:13937.
PMID: 26365497 DOI: 10.1038/srep13937

Homozygosity for the α-thalassaemia Southeast Asian (α-SEA) and Filipino β°-thalassaemia (β-FIL) deletions can cause serious complications leading to foetal death or life-long blood transfusions. A rapid and accurate molecular detection assay is essential in populations where the deletions are common. In this study, gap-polymerase chain reaction (PCR) with high resolution melting (HRM) analysis was developed to detect both the large deletions. Melting curves at 86.9 ± 0.1 °C were generated by normal individuals without the α-SEA deletion, 84.7 ± 0.1 °C by homozygous α-SEA deletion individuals and two melting curves at 84.7 ± 0.1 °C and 86.9 ± 0.1 °C by α-SEA deletion carriers. Normal individuals without the β-FIL deletion produce amplicons with a melting temperature (Tm) at 74.6 ± 0.1 °C, homozygous β-FIL individuals produce amplicons with Tm at 73.6 ± 0.1 °C and heterozygous β-FIL individuals generate two amplicons with Tm at 73.6 ± 0.1 °C and 74.6 ± 0.1 °C. Evaluation using blinded tests on 220 DNA samples showed 100% sensitivity and specificity. The developed assays are sensitive and specific for rapid molecular and prenatal diagnosis for the α-SEA and β-FIL deletions.

Matched MeSH terms: alpha-Thalassemia
Fulltext DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia

Tan JA, Kho SL, Ngim CF, Chua KH, Goh AS, Yeoh SL, et al.

Sci Rep, 2016 06 08;6:26994.
PMID: 27271331 DOI: 10.1038/srep26994

Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (α(codon 59)α/α(CS)α) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (α(codon 59)α/α(Paksé)α) after nine years of being misdiagnosis with Hb Adana and HbCS (α(codon 59)α/α(CS)α). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations.

Matched MeSH terms: alpha-Thalassemia/diagnosis*; alpha-Thalassemia/genetics
Fulltext Association of hematological analysis and α-globin genotypes among eligible blood donors in University Tunku Abdul Rahman (UTAR)

Lai Kuan Teh, Li Fang Lim, Yu Leong Teh, Tze Yan Lee, Lay Ngor Lim, Elizabeth George

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):48-48.
MyJurnal

Introduction: Reduction or complete absence of α-globin chain production may result α-thalassemia. Alpha thalassemia carrier may have normal haemoglobin level and thus will be eligible as blood donor. Few complications may happen in which the carrier who donated the blood might be at risk of hypoxia and their blood components might not suitable for transfusion. Thus, it is important to screen for α-thalassemia to prevent any complications happen
after donation. The objective of this study is to investigate the interaction of red blood cell indices and α-globin genotypes among eligible blood donors in a private university, Universiti Tunku Abdul Rahman (UTAR), Malaysia. Methods: A total of 270 eligible blood donors were recruited for this study. Red cell indices were analysed using Horiba hematology analyser and α-globin genotyping was performed for seven alpha deletions, six alpha point mutations
and two alpha triplications. Results: Our study showed high prevalence of α-thalassemia carriers among the eligible blood donors (7.7%, 21/270), with all of them showed normal Hb level (>12 gm/dl). Five genotypes were detected consisting of 249 αα/αα (92.2%), 9 -α3.7/αα (3.3%), 9 --SEA/αα (3.3%), 2 -α4.2/αα (0.7%) and 1 ααCS/αα (0.4%). All α-globin genotypes showed normal Hb level with no significant difference between genotypes (p=0.167). Different
α-globin genotypes showed significant difference in RBC, MCV, MCH, MCHC, RDW and Hct/Hb ratio at the p

Matched MeSH terms: alpha-Thalassemia

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