Non-invasive prenatal screening & diagnosis of ?-thalassaemia in an affected foetus

Background & objectives: Non-invasive prenatal testing (NIPT) of maternally inherited alleles of ?-thalassaemia (MIB) remains to be a challenge. Furthermore, current techniques are not available for use as routine tests. NIPT for ?-thalassaemia disease was developed by using a specific droplet digital polymerase chain reaction (ddPCR) assay to analyze the cell-free foetal DNA (cffDNA) derived from maternal plasma. Methods: Pregnant women and their spouses who are at risk of bearing an offspring with ?-thalassaemia disease from common MIB mutations (CD 41/42-TCTT, CD17A>T, IVS1-1G>T and CD26G>A) were enrolled. The ddPCR assay sets were constructed for each of the four mutations. All cell-free DNA samples were first screened for the paternally inherited ?-thalassaemia (PIB) mutation. The PIB-negative samples were considered as non-disease and were not further analyzed. For PIB-positive samples, DNA fragments of 50-300 base pairs in size were isolated and purified, and further analyzed for MIB mutation. The allelic ratio between the mutant and the wild-type was used to determine the presence of MIB in cffDNA. All cases underwent a prenatal diagnosis by amniocentesis for a definite diagnosis. Results: Forty two couples at risk were enrolled. Twenty two samples were positive for PIBs. Among these 22 samples, there were 10 cases with allelic ratio >1.0 (MIB positive). All foetuses with over-represented mutant alleles were further diagnosed with ?-thalassaemia disease; eight with compound heterozygous and two with homozygous mutations. The 20 PIB-negative and 12 MIB-negative foetuses were non-affected. Interpretation & conclusions: The results of this study suggest that NIPT utilizing the ddPCR assay can be effectively used for the screening and diagnosis of foetal ?-thalassaemia in at risk pregnancies.

An Effective Management for Thalassaemic Patients during Pregnancy

Background : Presence of thalassaemia is considered high risk in pregnancy. The present study find out the role of antenatal and intrapartum care to improve the outcome of pregnancy in thalassaemia. Materials and Method : The prospective longitudinal study was carried out on 25 patients. CBC, LFT, Ferritin, Hb electrophoresis, serial USG was done. Chorionic villous sampling was offered to thalassaemic women to decrease the number of babies born with Thalassaemia. Furthermore, management and treatment options provided to mother to overcome the incidence of maternal and neonatal complications during current pregnancy. Results : 44% of thalassaemic pregnant women had HbE ? thalassaemia, 8% ? thalassaemia major and others had thalassaemia carriers, while only 20% of their partners showed ? thalassaemia trait. All patients were anemic and during delivery mean Hb% were 8.42 g/dl, MCH 22.09 pg, MCV 73.56 fl, MCHC 29.86 g/dl and ferritin 241.51 ng/ ml. Third trimester USG exhibited 32% developed IUGR (Intrauterine growth restriction). 40% patients received blood transfusion after delivery. ? thalassaemia trait was identified in 20% babies at 6 month. Conclusion : Postpartum haemorrhage is a major complication of thalassaemia in pregnancy. After delivery a thorough neonatal check-up and haematological work-up is important for prevention of neonatal mortality and early detection of thalassaemia.

Reviewing the Compounding Risks for Tuberculosis DrugInduced Liver Injury in a Patient with Transfusion Dependent Thalassaemia

@#A patient presents with jaundice three weeks into commencement of anti-tuberculosis therapy (ATT). Tuberculosis drug-induced liver injury (TB-DILI) is a main concern in patients commencing ATT. Studies have reported various risk factors associated with TB-DILI, urging vigilance in monitoring liver enzymes in these patients. We aim to review the causes of jaundice in a patient with transfusion dependent thalassaemia commenced on ATT and highlight the risk factors associated with TB-DILI.

Clinical and Haematological Parameters of Commonly Reported Non-deletional α-thalassaemia Mutations in Southeast Asia: A Review

@#Alpha (α)-thalassaemia is a common genetic disorder worldwide caused by the deletion and rarely non-deletional mutations of the α-globin gene. Nearly 70 types of non-deletional mutations have been reported worldwide, and this review focuses on the common ones affecting α-thalassaemia patients. The common mutations are initiation codon mutation, codon 30, haemoglobin (Hb) Constant Spring, Hb Quang Sze, Hb Adana and Hb Evora. The haematological parameters of non-deletional mutations usually show mild changes. However, a severe reduction in haemoglobin level, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), and mean corpuscular haemoglobin count (MCHC) has been observed among compound heterozygous HbH disease, involving both deletional and non-deletional mutations. Although non-deletional mutations are rarely reported, it requires the study of more cases to understand the clinical phenotypes that lead to severe clinical manifestations.

Oral Health Status of Children with Thalassaemia in Melaka: A Pilot Study

ABSTRACT@#Thalassemia is an inherited disorder that involves abnormal haemoglobin formation. This cross-sectional study with universal sampling was conducted from May 2018 to January 2019 to evaluate the oral health status of children with thalassaemia. The sample consisted of 54 transfusion-dependent patients between the ages of 3–17 years old, who were registered at the paediatric day-care centre of Hospital Melaka. Oral health status was evaluated which included soft tissue examination, recording of dental caries, malocclusion and oral hygiene status of the children, while their parents answered a pre-validated self-administered questionnaire on sociodemographic and oral health practices and attitudes. The mean deft (decayed, exfoliated and filled teeth) among the 3–5 years old was 6.71±6.07. The mean DMFT (decayed, missing and filled teeth) was 3.00±3.94 among the 13–17 years old and 1.12±1.42 among the 6–12 years old. Most of the 3–5 years old children exhibited good oral hygiene (71.4%). Dentofacial findings among the 3–5 years old were increased overjet (35.7%) and open bite (28.6%) predominantly. Fractured teeth (69.2%), increased overjet (46.2%) and discolouration (23.1%) were the common dentofacial findings among the 6–12 years old while increased overjet (71.4%), soft tissue lesions (57.1%) and posterior crossbite (28.6%) were seen among the 13–17 years old. In this cohort of children with thalassaemia, the prevalence of dental caries was high in preschool children and older children.

Rare presentation of right Adrenal Mass: Extramedullary haematopoiesis in a patient with Thalassaemia Intermedia / Journal of the ASEAN Federation of Endocrine Societies

@#Extramedullary hematopoiesis (EMH) is a rare cause of adrenal mass. We present a 44-year-old woman who has thalassaemia intermedia, referred to Endocrinology clinic for huge adrenal mass. Along with a paraspinal lesion discovered in this patient, the leading diagnosis was EMH. The patient was treated with hypertransfusion and hydroxyurea, which led to a reduction in the size of the right adrenal mass and paraspinal mass. This case highlights the challenges in managing this rare condition. Although EMH is a rare cause of adrenal mass, the diagnosis must be considered in any patient with a history of a congenital hemolytic disorder, to avoid unnecessary surgical procedures.

Markers of ineffective erythropoiesis in non-transfusion dependent β-thalassaemia

@#Non-transfused β-thalassaemia patients develop complications related to unsuppressed ineffective erythropoiesis (IE). Serum markers of IE would be useful for risk stratification and monitoring treatment. We studied βthalassaemia trait (β-TT) and non-transfusion-dependent βthalassaemia (β-NTDT) patients. Serum erythropoietin (EPO) and soluble transferrin receptor (sTfR) were correlated against markers of clinical severity (haemoglobin, LDH, retics, bilirubin, spleen size) and iron overload (ferritin, hepcidin, and MRI-T2* in NTDT patients). Eleven β-NTDT and nine β-TT subjects were studied. βNTDT patients had significantly higher markers of haemolysis and iron overload. In β-NTDT, liver iron ranged from mild to severe, but no cardiac loading was seen. EPO and sTfR were higher in patients with β-NTDT than β-TT, and correlated significantly with each other (ρ=0.630, p=0.003). Both markers were negatively correlated with haemoglobin (sTfR ρ=-0.540, p=0.014; EPO ρ=-0.807, p<0.001, and positively correlated with spleen size (sTfR ρ=0.783, p<0.001; EPO ρ=0.654, p=0.002) and markers of iron overload. There was a strong correlation between ferritin and hepcidin (ρ=0.720, p<0.001), and a relatively lower increment of hepcidin for the degree of iron overload in βNTDT compared to β-TT. EPO and sTfR appear to be reliable markers of erythropoiesis in non-transfused β-thalassaemia and correlate well with markers of disease severity. Their role in managing patients, predicting complications, and monitoring response to treatments aimed at reducing IE should be explored.

Siriraj I Gγ(Aγδβ)0 -thalassaemia causing severe thalassaemia intermedia in compound heterozygous state with IVS1-1(G→T) mutation

@#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.

Detection of red cell alloantibodies in thalassaemia patients

Background: ?-thalassaemia patients receive regular blood transfusion to thrive. Due to antigen disparity between the blood donors and these patients they develop red cell alloantibodies due to alloimmunization.' The objective of this study is to predict the frequency of red cell alloimmunization amongst ?-thalassaemia major patients receiving regular blood transfusion.Methods: This study including 106 patients with ?-thalassaemia was conducted in the department of Transfusion Medicine, S. C. B. Medical College, Cuttack for a period of 12 months. Alloantibodies to different red cell blood group antigens in multi-transfused thalassaemia patients were detected using the glass bead technology for blood group serology in the present study.Results: Out of 106 ?-thalassaemia major patients included in the study, 7.5% of patients developed alloantibodies, all being clinically significant. The alloantibodies were anti-E, anti c, anti e and anti-D. The rate of incidence of these alloantibodies was 3.8%, 1.9%, 0.9% and 0.9% respectively.' There was a significant association between alloantibody formation with number of transfused packed red cells (Mann-Whitney Test: p value = 0.035) and age at first transfusion (p value = 0.001). The factors having no association with alloimmunization to red cell antigens are age and gender.Conclusions: Alloimmunization to various erythrocyte blood group antigens is a common problem in multi-transfused ?-thalassaemia patients. There is an association between number of transfused packed red cells and age at first transfusion with alloantibody formation in the study.

Microcytic to hypochromic ratio as a discriminant index of thalassaemia trait in subjects with hypochromic anaemia

@#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.

Transfusion Transmitted Malaria in a Thalassaemia Major Patient

@#Blood safety is a major global issue. Transfusion transmitted parasitic infections (TTPI) like malaria are rare and possibly under-reported, a situation which could be attributed to lack of awareness of the mosquito-borne transmission of infection. Such infections are still considered potential health hazards, as they can pose a significant threat especially in immunocompromised patients, where they have proven to be fatal. Prevention of the transmission depends solely on the donor’s questionnaire which addresses previous or current infection with aetiologic agents. Donor deferral is effective however clear guidelines are needed. This case report features the transfusion-transmitted of Plasmodium Falciparum in a 15-year-old splenectomised patient with underlying beta thalassaemia major.

Elucidating the Possible Mechanism of Renal Dysfunction in Alpha Thalassaemia: A Review

@#Recent improvement in the treatment and management of α-thalassaemia has enabled patients to live longer and have better quality of life, thus revealing other complications related to the disorder mainly due to the effects of chronic ineffective erythropoiesis and iron overload. We review the renal dysfunction seen in α-thalassaemia as it has been reported (published and personal communication) that the complications presented are more severe than those found in β-thalassaemia patients of similar severity clinically. This review aims to shed light on emerging complications that are currently faced by α-thalassaemia patients as they progress further in life

Optimal Mean Corpuscular Haemoglobin (MCH) Cut-Off Value for Differentiating Alpha Plus and Alpha Zero Thalassaemia in Thalassaemia Screening

@#Introduction: The aim of thalassaemia screening is to reduce thalassaemia syndromes with significant clinical implication. Therefore, detection of α0 thalassaemia with two genes deletion is clinically more important than α+ thalassaemia with one gene deletion. The aim of this study is to determine the mean corpuscular haemoglobin (MCH) cut-off point for α0 thalassaemia screening. Method: A total of 688 α0 and α+ thalassaemia cases confirmed by DNA analysis were analysed. Red cell indices (MCV, MCH, RBC, Hb) were retrieved from the laboratory information system. Receiver operating characteristic (ROC) curve is generated to determine the MCH cut-off point for α0 thalassaemia. The diagnostic performance of MCH cut-off value was evaluated with a validation group comprising 100 samples of alpha thalassaemia carriers. Results: ROC curve analysis with area under the curve (AUC) of 0.969 showed that MCH at cut-off of 23.5pg has high sensitivity and specificity in detecting α0 thalassaemia with 98% sensitivity and 85% specificity. Conclusion: MCH cut-off value of 23.5pg can be adopted as the cut-off point for α0 thalassaemia screening to detect clinically significant thalassaemia syndrome and reduce cost and burden of screening.

A link between long non-coding RNA (lncRNA) and thalassaemia: A review

@#The long non-coding RNAs (lncRNAs) are the most prevalent and functionally diverse member of the non-coding RNA (ncRNA). The lncRNA has previously been considered to be a form of transcriptional “noise” but recent studies have found that the lncRNA to be associated with various disease conditions. It has also been found to play important roles in various physiological processes such as haemopoiesis, where lncRNA is reported to act as a fine-tuner of this very important process. To date, the effects of dysregulated lncRNA in thalassaemia has not been fully explored. This review article focuses on the possible roles of dysregulated lncRNAs in the pathogenesis of thalassaemia.

Assessment of serum ferritin levels in transfusion dependent thalassemic children on oral deferiprone in a tertiary care centre

Background: Thalassemic patients require regular blood transfusions to maintain haemoglobin level around between 10gm/dl-15gm/dl, which would result in transfusional iron overload. The treatment of iron overload is carried out by using parenteral desferrioxamine (DFX) therapy or recently introduced oral Deferiprone (DFP,L1,Ferriprox,KELFER,CP20) an oral iron chelator, Oral deferiprone, DFP (3-hydroxy-1,2-dimethylpyridin-4-one) is a synthetic analogue of mimosine, an iron chelator isolated from the legume Mimosa paduca. Our study was undertaken to asses ferritin concentration in transfusion dependent thalassemic children on Deferiprone, attending thalassemia clinic in Anil Neerukonda hospital, Sanghivalasa, Visakhapatnam.Methods: The present study was a hospital based prospective study, 50 transfusion dependent thalassemic children on Deferiprone, attending thalassemia clinic in Anil Neerukonda hospital, Sanghivalasa, Visakhapatnam attached to NRI Medical College, Visakhapatnam were enrolled during the study period October 2017 and September 2018.Results: In our study authors found an increase in Serum ferritin concentration from 3067.99'1520.13 to 4281.10 '1760.42 ng/ml at the end of 12 months, which was quite significant.Conclusion: Authors concluded that oral Deferiprone is not an effective iron chelation agent and is associated with complications like GI symptoms, joint pains in significant number of children. So, search for an alternative iron chelator or combined chelation therapies which are safe and cost effective should be continued.

Wide range of F cell levels in healthy Thai adults: Influence of Swiss-type hereditary persistence of foetal haemoglobin & ?-haemoglobinopathy

Background & objectives: Swiss-type hereditary persistence of foetal haemoglobin (HPFH) has been shown to be responsible for the wide range of F cell levels in healthy Thai adults. However, a survey for F cells in healthy Thai adults has not been performed. This study was conducted to determine the F cell distribution in adult Thai blood donors and to assess the possible involvement of ?-thalassaemia and haemoglobin E (HbE) carriers in increased HbF levels. Methods: Thai blood donors (n=375, 205 males and 170 females) were included in the study. Blood samples were collected for measuring haemoglobin (Hb) concentration and haematocrit (Hct) and F cell levels. Hb and Hct levels were determined by automated blood counter, while F cells were quantified by flow cytometric analysis of F cells stained by fluorescein isothiocyanate-conjugated anti ?-globin monoclonal antibody. Finally, F cell levels were compared between blood samples having mean corpuscular volume (MCV ) <80 fl and ?80 fl as well as between ?-haemoglobinopathies (HbE and ?-thalassaemia carriers) and normal adults. Results: F cell levels varied markedly spanning 0.80-39.2 per cent with a positively skewed distribution. Thirty two per cent of these individuals had F cell levels more than the 4.5 per cent cut-off point. F cell levels in females were significantly higher than those in males (P<0.05). F cell levels in individuals having MCV <80 fl were significantly higher than those having MCV ?80 fl (P<0.05). ?-haemoglobinopathy (HbE and ?-thalassaemia carriers) had significantly higher F cell levels than normal individuals (P<0.05). Interpretation & conclusions: The present results showed that besides Swiss-type HPFH, the ?-haemoglobinopathy was expected to be involved in increased F cell levels in adult Thais. Thus, influence of ?-haemoglobinopathy must be considered in interpreting F cell levels in area endemic of this globin disorder.

Evaluation of efficacy of BIORAD D10TM testing system in detection of beta thalassaemia carrier

Background: Hemoglobinopathies especially thalassaemia and its interaction with HbE and HbS are significant cause of morbidity and mortality in our country. With no feasible treatment, prevention of cases by carrier detection is the only option for successful reduction of the disease burden. VARIANT hemoglobin testing system BIORAD using principle of cation exchange chromatography has been in use and considered as gold standard for carrier detection. The purpose of this study is to compare the efficacy of a different, cheaper instrument; D10 by the same manufacturer BIORAD for carrier detection in beta thalassaemia.Methods: Patients diagnosed as beta thalassaemia carrier by VARIANT hemoglobin testing system (HbA2 value between 4.0-9.0) were retested using D10 instrument and checked for agreement.Results: There was good correlation between VARIANT and D-10 methods with Intraclass correlation coefficient 0.832 (95% Confidence Interval 0.756-0.884). Bland-Altman analysis showed mean bias of +0.3526 (95% CI -0.3958 to +1.101).Conclusions: Although further study is needed with larger sample size for assessment of sensitivity and specificity of D10 instrument, it is evident from this study that this instrument can be an effective and cheaper alternative of VARIANT hemoglobin testing system.

Comparative study of alloimmunization against red cell antigens in sickle cell disease & thalassaemia major patients on regular red cell transfusion

Background & objectives: Sickle cell disease (SCD) patients require red cell transfusion during different clinical complications of the disease. Such patients are at a high risk for developing alloantibody against red cell antigens. From India, there are limited data available on alloantibody formation in multiply transfused SCD patients. The present study was thus undertaken to fill up this lacunae by looking at the development of red cell alloantibodies in SCD and ?-thalassaemia patients on regular transfusion. Methods: All sickle cell disease patients undergoing red cell transfusion between 2008 and 2016, were included. During this period, a large number of ?-thalassaemia major patients also underwent regular red cell transfusion. These thalassaemia patients were also included to compare the tendency of antibody formation between SCD and ?-thalassaemia major patients. All patients before regular transfusion were regularly assessed for the development of red cell antibody. Red cell antigen, antibody screen crossmatch and antibody identification were done using the standard technique. Results: A total of 138 patients with SCD aged between 4 and 53 yr (mean 17.6 yr) consisting of 83 males and 55 females (male:female, 1.5:1) along with 333 transfusion-dependent ?-thalassaemia patients were studied. Over the last eight years, 15 patients with SCD and four patients with thalassaemia developed alloantibody (P <0.001). Antibody specificity of their alloantibodies was against Rhc, RhE, Kell, Fya and Fyb only. Sickle cell disease patients with and without alloantibody required on the average 11.8 and 8.6 units of red cell concentrate, respectively (P <0.05). Interpretation & conclusions: About 11 per cent of the transfused sickle cells patients developed alloantibodies. The antibody specificity was restricted to Rh, Kell and Duffy blood group systems. Extended antigen matching involving Rh, Kell and Duffy antigens may prevent alloantibody in such patients.

LARP2 DNA Methylation in Transfusion-dependent Haemoglobin E-Beta (HbE/β) and β-Thalassaemia Major Patients

Abstract@#Introduction: The large clinical spectrum of haemoglobin E-beta (HbE/β) thalassaemia leads to the investigation of complex mechanisms involved in erythropoiesis. DNA methylation in LARP2 is one of the potential epigenetic modifiers not fully explored in HbE/β and β-thalassaemia major. This study aimed to analyse DNA methylation profile and gene expression of LARP2 using peripheral blood (PB) in nucleated red blood cells (NRBCs) for the source of DNA of HbE/β- and β-thalassaemia major patients. Methods: PB were collected from 33 transfusion-dependent thalassemia patients from Hospital USM and Hospital RPZII, Kelantan, Malaysia. DNA methylation profile and gene expression of LARP2 were examined by bisulphite sequencing PCR and quantitative real-time PCR respectively. Results: Partial DNA methylation of LARP2 was observed in 43% (9/21) HbE/β- and 17% (2/12) β-thalassaemia major patients. LARP2 expression (1.49±26.60) in HbE/β-thalassaemia was not significant against normal controls and β-thalassaemia major (p>0.05). In contrast, LARP2 expression (6.8±16.42) in β-thalassaemia major showed a significant up-regulation against normal controls (p<0.05). The association of LARP2 expression and DNA methylation profile was statistically significant (p<0.001). LARP2 expression was down-regulated in 75% (3/4) HbE/β-thalassaemia patients with CD26/IVS1-5, in contrast to up-regulation of 80% (4/5) IVS1-5/IVS1-5 β-thalassaemia major patients. DNA methylation of LARP2 in these patients were either partially methylated or unmethylated in CD26/IVS1-5 and IVS15/IVS1-5 respectively. Conclusion: DNA methylation of LARP2 may act as an additional modifier to gene mutation especially involving IVS1-5 in HbE/β-thalassaemia. Homozygous IVS1-5 in β-thalassaemia major may contribute to different disease presentation compared to those involving CD26 in HbE/β-thalassaemia.

Prevalence of growth and endocrine disorders in Malaysian children with transfusion-dependent thalassaemia

INTRODUCTION@#Endocrine dysfunction due to iron overload secondary to frequent blood transfusions is a common complication in children with transfusion-dependent thalassaemia (TDT). We ascertained the prevalence of endocrine dysfunction in children with TDT seen in a hospital setting in Malaysia.@*METHODS@#We reviewed all patients with TDT who had ≥ 8 blood transfusions per year. Patients who had a history of stem cell transplantation, concurrent autoimmune diseases or were newly diagnosed to have TDT were excluded. Standard diagnostic criteria were used in the diagnosis of various endocrine dysfunctions.@*RESULTS@#Of the 82 patients with TDT, 65% had at least one endocrine dysfunction. Short stature was the commonest (40.2%), followed by pubertal disorders (14.6%), hypoparathyroidism (12.3%), vitamin D deficiency (10.1%), hypocortisolism (7.3%), diabetes mellitus (5.2%) and overt hypothyroidism (4.9%). Subclinical hypothyroidism and pre-diabetes mellitus were seen in 13.4% and 8.6% of the patients, respectively. For children aged 10 years of age. Close monitoring for endocrine dysfunction and hormonal therapy is essential to prevent long-term adverse outcomes.