Research progress of iron metabolism in phenotype modification of β-thalassemia / 中华医学遗传学杂志

β-thalassemia is a type of inherited hemolytic anemia caused by decreased globin production due to defect of the HBB gene. The pathogenesis of the disease is imbalance of α/β globin chains. The excess of α-globin chains will form hemichromes which can damage red blood cell membranes and lead to hemolysis, ineffective erythropoiesis, and secondary iron overload. Iron overload in turn can cause complications such as growth retardation, liver cirrhosis, cardiac insufficiency, and aggravate the disease phenotype. In recent decades, genes participating in iron metabolism have been discovered, and the mechanism of iron metabolism in the development of thalassemia has gradually been elucidated. Subsequently, by manipulating the expression of key genes in iron metabolism such as hepcidin and transferrin receptor, researchers have revealed that iron restriction can improve ineffective hematopoiesis and iron overload, which may provide a potential approach for the treatment of thalassemia. This article reviews the progress of research on iron metabolism-related genes and related pathways in β-thalassemia.

Vascular endothelial growth factor and pulmonary hypertension in children with beta thalassemia major / Fator de crescimento endotelial vascular e hipertensão pulmonar em crianças com talassemia beta maior

Abstract Objective: The purpose of this study was to illustrate the association between vascular endothelial growth factor level and pulmonary artery hypertension in children with β-thalassemia major. Method: This case-control study was conducted on 116 children with β-thalassemia major; 58 of them had pulmonary artery hypertension. They were compared to 58 healthy children who were age and sex-matched (control group). Serum levels of vascular endothelial growth factor and echocardiographic assessment were done for all children. Results: Vascular endothelial growth factor serum level was significantly higher in children with β-thalassemia major with pulmonary artery hypertension than in those without pulmonary artery hypertension, as well as in control groups (p < 0.001). Vascular endothelial growth factor serum level had a significant positive correlation with pulmonary artery pressure and serum ferritin, as well as a significant negative correlation with the duration of chelation therapy. Logistic regression analysis revealed that elevated vascular endothelial growth factor (Odd Ratio = 1.5; 95% Confidence Interval, 1.137-2.065; p = 0.005) was an independent risk factor of pulmonary artery hypertension in such children. Vascular endothelial growth factor serum level at a cutoff point of >169 pg/mL had 93.1% sensitivity and 93.1% specificity for the presence of pulmonary artery hypertension in children with β-thalassemia major. Conclusion: Elevated vascular endothelial growth factor serum level is associated with pulmonary artery hypertension in children with β-thalassemia.

Resumo: Objetivo: A finalidade deste estudo foi exemplificar a associação entre o nível de fator de crescimento endotelial vascular e a hipertensão arterial pulmonar em crianças com talassemia beta maior. Método: Este estudo caso-controle foi realizado em 116 crianças com talassemia beta maior; 58 das quais apresentaram hipertensão arterial pulmonar em comparação com 58 crianças saudáveis pareadas por idade e sexo (grupo de controle). Os níveis séricos do fator de crescimento endotelial vascular e a avaliação ecocardiográfica foram realizados em todas as crianças. Resultados: O nível sérico do fator de crescimento endotelial vascular foi significativamente maior em crianças com talassemia beta maior com hipertensão arterial pulmonar que as crianças sem hipertensão arterial pulmonar e os grupos de controle (p < 0,001). O nível sérico do fator de crescimento endotelial vascular apresentou uma correlação positiva significativa com a pressão arterial pulmonar e a ferritina sérica e correlação negativa significativa com a duração da terapia de quelação. A análise de regressão logística revelou que o fator de crescimento endotelial vascular elevado (RC = 1,5; IC de 95%: 1,137-2,065; p = 0,005) foi um fator de risco independente de hipertensão arterial pulmonar nessas crianças. O nível sérico do fator de crescimento endotelial vascular no ponto de corte > 169 (pg/mL) apresentou 93,1% de sensibilidade e 93,1% de especificidade na presença de hipertensão arterial pulmonar em crianças com talassemia beta maior. Conclusão: O nível sérico do fator de crescimento endotelial vascular elevado está associado à hipertensão arterial pulmonar em crianças com talassemia beta.

Intraocular pressure in subjects with beta-thalassemia minor / Pressão intraocular em indivíduos com talassemia beta minor

ABSTRACT Purpose: Beta-thalassemia minor, a common hereditary blood disorder in Mediterranean countries such as Turkey, is associated with insulin resistance. Insulin resistance, in turn, can be associated with excessively high intraocular pressure and, therefore, intraocular pressure-induced blindness. This study aimed to investigate the intraocular pressure in subjects with beta-thalassemia minor. Methods: We conducted a cross-sectional study comprising of 203 subjects divided into two groups: beta-thalassemia minor (103) and healthy (100).Hemoglobin electrophoresis was performed and complete blood count, blood pressures, serum fasting glucose and insulin levels were measured. All subjects underwent ophthalmological examinations including intraocular pressure measurements. Results: Intraocular pressure in the subjects with beta-thalassemia minor was significantly lower than that in healthy subjects (p=0.007). Additionally, intraocular pressure was inversely correlated with hemoglobin A2 levels (p=0.001, r=-0.320). Serum insulin and systolic blood pressure were significantly higher in subjects with beta-thalassemia minor (p=0.03, p=0.009, respectively). Conclusion: Subjects with beta-thalassemia minor had lower intraocular pressure than healthy controls, suggesting beta-thalassemia minor may actually protect against high intraocular pressure.

RESUMO Objetivo: Beta-talassemia menor é uma doença hereditária comum no sangue em países mediterrâneos como a Turquia e está associada à resistência à insulina. A resistência à insulina por sua vez, pode estar associada à pressão intraocular excessivamente alta e, portanto à cegueira induzida pela pressão intraocular. Este estudo teve como objetivo investigar a pressão intraocular em indivíduos com beta-talassemia menor. Métodos: Foi realizado um estudo transversal compreendendo 203 indivíduos divididos em 2 grupos: beta-talassemia menor (103) e saudável (100). Eletroforese de hemoglobina foi realizada e hemograma completo, pressão arterial, glicemia em jejum e níveis de insulina medidos. Todos os indivíduos foram submetidos foram submetidos a exames oftalmológicos, incluindo medidas de pressão intraocular. Resultados: A pressão intraocular nos indivíduos com beta-talassemia menor foi significativamente menor do que em indivíduos saudáveis (p=0,007). Além disso, a pressão intraocular foi inversamente correlacionada com os níveis de hemoglobina A2 (p=0,001, r=-0,320). Insulina sérica e pressão arterial sistólica foram significativamente maiores em indivíduos com beta-talassemia menor (p=0,03, p=0,009, respectivamente). Conclusão: Os indivíduos com beta-talassemia menor tiveram pressão intraocular menor do que os controles saudáveis, sugerindo que a beta-talassemia menor pode, na verdade, proteger contra a alta pressão intraocular.

Ecocardiografia de pacientes talassêmicos sem insuficiência cardíaca em tratamento com transfusões sanguíneas e quelação / Echocardiography in thalassemic patients on blood transfusions and chelation without heart failure

FUNDAMENTO: Pacientes com talassemia major (TM) apresentam hemólise crônica e necessitam de transfusões sanguíneas egularmente que podem causar cardiomiopatia por sobrecarga de ferro e insuficiência cardíaca crônica. A hemocromatose é caracterizada por acúmulo excessivo de ferro nos tecidos; acometimento do coração é a principal causa de óbito em pacientes com talassemia. OBJETIVO: Avaliar as estruturas e a função cardíaca por meio de ecocardiografia com Doppler convencional e Doppler tecidual em pacientes com TM, sem evidência clínica de insuficiência cardíaca. MÉTODOS: Trata-se de estudo observacional prospectivo de 18 pacientes com TM que recebem transfusão sanguínea regularmente. Para avaliar, separadamente, os efeitos da anemia e da transfusão sanguínea, dois grupos controles pareados por gênero, idade, peso e altura foram incluídos: um com indivíduos saudáveis (Saudável, n = 18) e outro com pacientes com anemia por deficiência de ferro (Anemia, n = 18). Análise estatística foi realizada utilizando ANOVA seguida pelo teste de Tukey ou Kruskal-Wallis e teste de Dunn. RESULTADOS: As seguintes variáveis ecocardiográficas apresentaram valores significativamente mais elevados no grupo TM do que nos grupos Anemia e Saudável: índice de volume do átrio esquerdo (Saudável: 16,4 ± 6,08; Anemia: 17,9 ± 7,02; TM: 24,1 ± 8,30 cm/m); razão E/Em septal mitral (Saudável: 6,55 ± 1,60; Anemia: 6,74 ± 0,74; TM: 8,10 ± 1,31) e duração do fluxo reverso em veias pulmonares [Saudável: 74,0 (59,0-74,0); Anemia: 70,5 (67,0-74,0); TM: 111 (87,0-120) ms]. Arazão E/A mitral foi maior no grupo TM do que no grupo Anemia (Saudável: 1,80 ± 0,40; Anemia: 1,80 ± 0,24; TM: 2,03 ± 0,34). Não foram encontradas diferenças entre os grupos em variáveis estruturais do ventrículo esquerdo e em índices de função sistólica. CONCLUSÃO: A ecocardiografia com Doppler convencional e o Doppler tecidual permite que alterações na função diastólica do ventrículo esquerdo sejam identificadas em pacientes assintomáticos com talassemia major.

BACKGROUND: Patients with thalassemia major present chronic hemolysis and require regular blood transfusions which may cause iron overload cardiomyopathy and chronic heart failure. Hemochromatosis is characterized by excessive iron accumulation in tissues, and heart involvement is the main cause of death in patients with thalassemia. OBJECTIVE: The aim of this study was to evaluate cardiac structure and function by conventional Doppler echocardiography and tissue Doppler imaging in patients with TM and no clinical evidence of heart failure. METHODS: This is a prospective observational study including 18 patients with thalassemia major (TM) receiving regular blood transfusion. To separately evaluate anemia and blood transfusion effects, two gender, age, weight, and height-matched control groups were included: one with healthy individuals (Healthy, n=18) and one with iron deficient anemia patients (Anemia, n=18). Statistical analysis was performed using ANOVA followed by Tukey's test or Kruskal-Wallis's and Dunn's test. RESULTS: The following echocardiographic variables presented significantly higher values in TM than the Anemia and Healthy groups: left atrium volume index (Healthy: 16.4±6.08; Anemia: 17.9±7.02; TM: 24.1±8.30 cm³/m²); mitral septal E/Em ratio (Healthy: 6.55±1.60; Anemia: 6.74±0.74; TM: 8.10±1.31); and duration of reverse pulmonary vein flow [Healthy: 74.0 (59.0-74.0); Anemia: 70.5 (67.0-74.0); TM: 111 (87.0-120) ms]. The mitral E/A ratio was higher in TM than Anemia (Healthy: 1.80±0.40; Anemia: 1.80±0.24; TM: 2.03±0.34). No differences were found in left ventricular structures and systolic function indexes. CONCLUSION: Conventional Doppler echocardiography and tissue Doppler allow changes in left ventricular diastolic function to be identified in asymptomatic patients with thalassemia major.

Antioxidant status in beta thalassemia major: A single-center study.

Background: Homozygous β thalassemia may lead to a marked reduction or absence of normal β chain production and accumulation of unpaired alpha-globin chains. A crucial component in the oxidant susceptibility of the thalassemic RBC is the release of heme and iron from the excessive, unpaired α-globin chains. This release can initiate self-amplifying redox reactions, which deplete the cellular reduction potential (e.g., GSH), oxidize additional hemoglobin and accelerate RBC destruction. Furthermore, β-thalassemia patients are under continuous blood transfusion, which, although life-saving, leads to an iron overload with a resultant increase in non-transferrin-bound iron that may cause greater tissue toxicity than iron in other forms. Iron-induced oxidative stress is known to be one of the most important factors determining cell injury in thalassemic patients. Therefore, we designed this study to obtain a comprehensive picture of the iron overload, antioxidant status and cell damage in β thalassemia major patients undergoing regular blood transfusion. Materials and Methods: A total of 48 diagnosed patients of β thalassemia major and 30 age- and sex-matched healthy subjects were included in the study. Estimation of hemoglobin, hematocrit, glutathione peroxidase (GPX), superoxide dismutase (SOD),vitamin E, serum ferritin, total and direct bilirubin, AST and ALT was carried out. Results: The levels of vitamin E, antioxidant enzymes GPX and SOD were significantly lowered in β thalassemic patients as compared with the control group (P<0.001). Serum total and direct bilirubin, AST and ALT were significantly elevated in thalassemic subjects as compared with the control group, indicating liver cell damage. Conclusion: Thus, our findings indicate that thalassemics are in a state of enhanced oxidative stress and that the administration of selective antioxidants would represent a promising approach toward counteracting oxidative damage and its deleterious effects on the disease status.

Results from transcranial Doppler examination on children and adolescents with sickle cell disease and correlation between the time-averaged maximum mean velocity and hematological characteristics: a cross-sectional analytical study / Resultados do estudo do Doppler transcraniano em crianças e adolescentes portadores de doença falciforme e correlação entre a velocidade média máxima e características hematológicas: um estudo transversal analítico

CONTEXT AND OBJECTIVE: Transcranial Doppler (TCD) detects stroke risk among children with sickle cell anemia (SCA). Our aim was to evaluate TCD findings in patients with different sickle cell disease (SCD) genotypes and correlate the time-averaged maximum mean (TAMM) velocity with hematological characteristics. DESIGN AND SETTING: Cross-sectional analytical study in the Pediatric Hematology sector, Universidade Federal de São Paulo. METHODS: 85 SCD patients of both sexes, aged 2-18 years, were evaluated, divided into: group I (62 patients with SCA/Sß0 thalassemia); and group II (23 patients with SC hemoglobinopathy/Sß+ thalassemia). TCD was performed and reviewed by a single investigator using Doppler ultrasonography with a 2 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. The hematological parameters evaluated were: hematocrit, hemoglobin, reticulocytes, leukocytes, platelets and fetal hemoglobin. Univariate analysis was performed and Pearson's coefficient was calculated for hematological parameters and TAMM velocities (P < 0.05). RESULTS: TAMM velocities were 137 ± 28 and 103 ± 19 cm/s in groups I and II, respectively, and correlated negatively with hematocrit and hemoglobin in group I. There was one abnormal result (1.6 percent) and five conditional results (8.1 percent) in group I. All results were normal in group II. Middle cerebral arteries were the only vessels affected. CONCLUSION: There was a low prevalence of abnormal Doppler results in patients with sickle-cell disease. Time-average maximum mean velocity was significantly different between the genotypes and correlated with hematological characteristics.

CONTEXTO E OBJETIVO: Doppler transcraniano (DTC) detecta risco de acidente vascular cerebral (AVC) em crianças com anemia falciforme (AF). O objetivo foi avaliar os resultados ao DTC nos diferentes genótipos da doença falciforme (DF) e correlacionar a velocidade média-máxima (VMMáx) às características hematológicas. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado no setor de Hematopediatria da Universidade Federal de São Paulo. MÉTODOS: 85 pacientes com DF, 2-18 anos, ambos os sexos, foram avaliados e divididos em: grupo I (62 com AF ou Sß0 talassemia); e grupo II (23 com hemoglobinopatia SC ou Sß+ talassemia). DTC foi realizado e revisado por um único investigador usando um aparelho de ultrassonografia Doppler com transdutor de 2MHz, conforme critérios do protocolo STOP (Stroke Prevention Trial in Sickle Cell Anemia). As variáveis hematológicas avaliadas foram: hematócrito, hemoglobina, reticulócitos, leucócitos, plaquetas, hemoglobina fetal. Análise univariada e coeficiente de Pearson calculados para parâmetros hematológicos e VMMáx, P < 0,05. RESULTADOS: As média das VMMáx foram de 137 ± 28 cm/s e 103 ± 19 cm/s nos grupos I e II, respectivamente. Houve correlação negativa da VMMáx com hematócrito e hemoglobina no grupo I. Houve um (1,6 por cento) resultado anormal e 5 (8,1 por cento) condicionais no grupo I; no grupo II, todos estavam normais. Artérias cerebrais médias foram as únicas acometidas. CONCLUSÃO: Houve baixa prevalência de resultados anormais ao DTC em pacientes com DF. A VMMáx foi significativamente diferente entre os genótipos da DF e apresentou correlação com variáveis hematológicas.

Marcadores eletrocardiográficos para detecção precoce de doença cardíaca em pacientes com talassemia beta maior / Electrocardiographic markers for the early detection of cardiac disease in patients with beta-thalassemia major

OBJETIVO: Analisar comparativamente a dispersão da onda P (DOP) em pacientes com talassemia beta maior (β-TM) e indivíduos saudáveis (controles) para a detecção precoce do risco de arritmias. MÉTODOS: Oitenta e uma crianças com β-TM, com idades entre 4 e 19 anos, e 74 crianças saudáveis (grupo controle) foram submetidas a exame eletrocardiográfico e ecocardiograma transtorácico de rotina para avaliação cardíaca. A DOP foi calculada como a diferença entre as durações máxima e mínima da onda P. RESULTADOS: Houve uma diferença estatisticamente significativa entre o grupo de estudo e o grupo controle no pico de velocidade do fluxo transmitral no início da diástole (E) e na razão E/fluxo transmitral tardio (A). A duração máxima da onda P e a DOP foram significativamente maiores nos pacientes com β-TM do que nos indivíduos controles. CONCLUSÕES: O aumento da DOP em nossos pacientes com β-TM pode estar relacionado à depressão na condução intra-atrial, devido à dilatação atrial, e ao aumento da atividade simpática. Estes pacientes devem ser acompanhados atentamente devido à possibilidade de ocorrência de arritmias com risco de vida.

OBJECTIVE: To comparatively evaluate P-wave dispersion (PWD) in patients with β-thalassemia major (TM) and healthy control subjects for the early prediction of arrhythmia risk. METHODS: Eighty-one children with β-TM, aged 4-19 years, and 74 healthy children (control group) underwent routine electrocardiography and transthoracic echocardiography for cardiac evaluation. PWD was calculated as the difference between the maximum and the minimum P-wave duration. RESULTS: There was a statistically significant difference between study and control groups in peak early (E) mitral inflow velocity and E/late (A) velocity ratio. Maximum P-wave duration and PWD were found to be significantly higher in β-TM patients than in control subjects. CONCLUSIONS: Increased PWD in our β-TM patients might be related to depression of intra-atrial conduction due to atrial dilatation and increased sympathetic activity. These patients should be closely followed up for risk of life-threatening arrhythmias.

Bone mineral density and vitamin d receptor polymorphism in beta-thalassemia major

Osteoporosis is the most prevalent bone complication in beta-thalassemic patients despite regular transfusions and iron chelation therapy. Although its etiology is multi-factorial, genetic factors play an important role in pathogenesis. These factors have not yet been clearly defined, however, osteoporosis may be related to vitamin D receptor gene BsmI polymorphism. In this study, BsmI vitamin D receptor gene polymorphism was analyzed using polymerase chain reaction and BsmI restriction fragment length polymorphism in 42 regularly treated- beta-thalassemic patients of different ages. Bone mineral density was measured by peripheral quantitative ultrasound at the heel of the foot. Serum levels of alkaline phosphatase, calcium, phosphorus, ferritin and 25-hydroxyvitamin D[3] were determined. Patients were divided into two groups according to pubertal signs: group I [22 children], and group II [20 adolescents and adults]. The Z-scores of bone mineral density in both groups were -1.32 +/- -0.9 and -2.30 +/- -1.02 respectively, with a significant difference between the two groups. The height standard deviation and 25-hydroxyvitamin D[3] were significantly decreased in group II compared to group I. Moreover, significantly lower bone mineral density and height standard deviation were detected among patients with BB vitamin D receptor genotype. Therefore, this genotype may be considered as a risk factor for osteoporosis in p-thalassemic patients

Growth velocity in transfusion dependent prepubertal thalassemia patients: results from a thalassemia center in Malaysia.

Growth impairment is commonly seen in children with thalassemia despite regular blood transfusions and desferrioxamine treatments. We investigated the growth velocity of 26 prepubertal patients with beta-thalassemia or HbE-beta thalassemia who were transfusion dependent aged between 2 and 13 years. The prevalence of impaired growth velocity (ie, growth velocity less than the third percentile) amongst the transfusion dependent prepubertal thalassemics was 57.7% compared to 19.2% in the control group. The mean height velocity of the thalassemics was 11.1% less than controls but this difference was not statistically significant (4.23cm/year vs 4.76cm/year, p = 0.08). The mean serum ferritin level of the thalassemics with a height < 3rd percentile was higher compared to those with a height > 3rd percentile (4,567.0 vs 2,271.0, p = 0.01). Our study showed that there was a high prevalence of impaired growth velocity amongst our transfusion dependent prepubertal thalassemics. This highlights the problem of inadequate chelation therapy, and compliance with chelation therapy amongst our patients. This study emphasizes the importance of monitoring growth parameters and optimal iron chelation therapy in these patients.

Genética das doenças hematológicas: as hemoglobinopatias hereditárias: [revisão] / The genetics of blood disorders: hereditary hemoglobinopathies: [review]

OBJETIVO: Sumarizar os dados disponíveis na literatura recente sobre os aspectos fisiopatológicos, de diagnóstico e tratamento das doenças falciformes e da talassemia β, hemoglobinopatias hereditárias de maior relevância nas populações. FONTES DOS DADOS: MEDLINE e SciELO, utilizando os termos hemoglobinopatias hereditárias, doenças falciformes e talassemia beta, no período de 2003 a maio de 2008. Dois livros e dois capítulos de livro foram também incluídos. SÍNTESE DOS DADOS: Foram encontrados mais de 2.000 artigos, sendo selecionados aqueles de maior pertinência e amplitude. CONCLUSÕES: As taxas de morbidade e a mortalidade das doenças falciformes e da talassemia β são ainda bastante expressivas e constituem importante desafio. Um maior conhecimento dos mecanismos fisiopatológicos tem permitido avanços significativos nas formas de tratamento e prevenção dessas doenças.

OBJECTIVE: To summarize recently published data on the pathophysiology, diagnosis and treatment of sickle cell diseases and β-Thalassemias, the most relevant hereditary hemoglobinopathies in the global population. SOURCES: Searches were run on the MEDLINE and SCIELO databases, limited to the period from 2003 to May 2008, using the terms hereditary hemoglobinopathies, sickle cell diseases and β-thalassemia. Two books and two chapters were also included. SUMMARY OF THE FINDINGS: More than 2,000 articles were identified; those providing the most important information and broadest views were selected. CONCLUSIONS: Morbidity and mortality rates from sickle cell diseases and β-thalassemia are still very high and represent an important challenge. Increased understanding of pathophysiological aspects has lead to significant improvements in treatment and prevention of these diseases.

Diagnostic validity of electrocardiography compared with echocardiography for diagnosing left ventricular hypertrophy in patients with beta-thalassemia major

Left ventricular hypertrophy [LVH] is an important risk factor in determining cardiovascular disease prognosis. Echocardiography [ECHO] is a sensitive and specific tool for detection of LVH but cost and operational consideration tend to limit its utility; in contrast, the Electrocardiography [ECG] is widely available, expensive and less operator dependent. Since the comparison of diagnostic validity between ECG and ECHO for evaluating of LVH has not been well studied, this survey was carried out on a number of major beta-thalassemia patients. This descriptive-analytical study was performed on 135 patients [including male and female] with major beta- thalassemia over 8 years old. Patients with heart failure, valvular or structural heart disease, renal and endocrine disease and Hb<10g/dl were excluded. ECG and ECHO were performed 48 h after blood transfusion. ECG criteria of LVH and myocardial performance index [MPI] in ECHO were measured. Sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV] of ECG indexes were calculated separately for both sexes and compared with ECHO findings. The patients included 64 [47/4%] males and 71 [52/6%] females. ECG indexes were found as follows: 70% sensitivity of the Sokolow-Lyon index, 14.3%; specificity, 90.3% PPV, 40% NPV and. Sensitivity of the Sokolow-Lyon-Rappaport, specificity, PPV, and NPV were 61.9%, 25/8%, 27/4%, 60%, respectively. Sensitivity of the Cornell index was66.6%. specificity 13.3%, PPV 86% and NPV 4.7%, Sensitivity of the White-Bock index was 0%, specificity 100%, PPV 0% and NPV was 68.9%. There was significant relationship between ECG indexes and some ECHO parameters. In this study there was a reverse and significant relationship between left acceleration time [AT] and the Sokolow-Lyon-Rappaport index statistically [r = 0.181, p = 0.035]. There was a significant direct relationship between left deceleration time [DT] and the Sokolow-Lyon-Rappaport index [r = 0.181, p = 0.036]. A reverse significant relationship between right AT and the Sokolow-Lyon index was seen [r = 0.173, p = 0.044]. A direct and significant relationship between diastolic inter ventricular septum diameter [IVSd] and the Sokolow-Lyon-Rappaport index was also observed [r = 0.186, p = 0.031]

Common queries in thalassemia care.

Beta thalassemia is a common genetic disorder in Indians. Around 10,000 thala-ssemia major cases are born every year. The treatment of thalassemia major patients imposes a financial burden on the family. Much progress has been made in last 15 years in understanding of the pathogenesis of thalassemia and development of effective management(1). These include development of a promising new oral iron chelator, intensive preparative regimens for stem cell transplantation and better vectors for gene therapy. In the present article, we highlight the common questions asked by the family and the general practitioners on thalassemia care.

Short stature, body disproportion, and endocrine disorders in thalassemia major

short stature and endocrine disorders are common compications of beta thalassemia major [TM]. The aim of this study was to determine the prevalence and causes of short stature, body disproportion, delayed puberty, and skeletal changes among thalassemia patients in our area. Patients and a prospective study was done on 314 patients with TM, randomly chosen at the Thalassemic Treatment Center of Al Yarmook Teaching Hospital during the period from January 2, 2001 to April 30, 2001. Patients ranged from 2-20 years of age and were divided into 5 groups. The male to female ratio was 1.2:1. The study included measurements of standing height, ratio of upper body to lower segment, puberty staging according to Tanner staging. Estimation of the hormones for which assays were available including growth hormone, T4, TSH, LH, and FSH were performed. The liver enzymes AST and ALI, and serum calcium were measured. Radiographs of the head, long bones, vertebrae, and wrist joints were done. The abnormalities noted were correlated with the duration of the DFX chelation and serum ferritin levels. the study revealed that 28% of the patients exhibited short stature, predominantly in the age group 15-20 years, and 25% of the patients had short trunk but normal stature predominantly in the age group of 10-14. There was a significant relation to the duration of DFX chelation, p=0.0004. Delayed puberty was present in 33/63 patients [52.4%; 19 were females [57.5%] and 14 were males [42.5%]. Endocrine disorders were present in 25.9%. Hypogonadotropic hypogonadism and hypocalcemia were present in 8.4% and 12% of the patients respectively. There was a significant relation to the duration of the disease, p=0.00003 and 0.0004 respectively. Skeletal changes including platyspondylosis, maxillary overgrowth, hair-on-end appearance, rectangular metacarpals and metatarsals, and osteoporosis were found in 38.6% of the patients in the age group of 10-14 years and were significantly related to the duration of DFX chelation, p=0.0001. short stature, short trunk, skeletal changes and delayed puberty are significant problems in our thalassemic patients. The role of siderosis and DFX toxicity need further elucidation

Pulmonary function tests in beta thalassemia.

To study pulmonary function tests (PFT) in multiple transfusion recipient thalassemics, PFTs were done for 30 thalassemics and 20 matched controls. Confirmed cases of thalassemia on regular transfusion therapy were the subject of study. Apart from history and physical examination of the thalassemics, serum ferritin estimation and spirometry were done. Parameters studied included lung volumes--functional residual capacity (FRC), forced vital capacity (FVC), residual volume (RV) and total lung capacity (TLC); and flow rates--forced expiratory volume in one second (FEV1), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), peak expiratory flow 25-75 (PEF 25-75%) and peak expiratory flow rate (PEFR). Single breath carbon monoxide diffusing capacity (DLco) and arterial blood gas (ABG) were also analysed. The mean height and weight of thalassemics were below that of age matched controls. A restrictive abnormality in PFT was found in 86.6% cases. These patients were found to have a decrease in all the lung volumes namely FVC, FRC, RV and TLC with a proportional decrease in the flow rates, FEV1, PEF 25-75% and PEF with a normal (> 0.75) FEV1/FVC ratio. DLco was decreased in all the patients with restrictive lung disease and fall in DLco showed a good correlation (r = 0.7, P < .001) with the severity of restrictive disease suggesting that some intrapulmonary pathology is likely to be responsible for the restrictive pattern. None of the cases had an obstructive or mixed pattern of pulmonary dysfunction. No correlation was found between severity of restrictive disease and the serum ferritin levels. A negative correlation with degree of hepatosplenomegaly was found. No correlation was found between severity of the defect and age, number of blood transfusions received and hemoglobin at the time of doing the test. To conclude, restrictive lung disease is the predominant abnormality in multi-transfused thalassemics, which is probably due to pulmonary parenchymal pathology. The abnormality of PFTs is not directly related to iron overload.

Scintigraphic evaluation of bone involvement in beta thalassemia major

En este artículo los autores presentan el caso de un hombre de 19 años de edad portador de beta talasemia mayor que fue referido para cintigrafía ósea con Tc99m metilendifosfonato (Tc99m MDP) por un cuadro de lumbalgia. Este caso muestra muchas de las repercusiones de la beta talasemia mayor en el esqueleto. Además, podemos observar signos indirectos de algunas endocrinopatías asociadas

Echocardiographic features in patients with beta thalassemia/hemoglobin E: a combining effect of anemia and iron load.

Hemoglobin concentration, iron parameters and cardiac status of 25 patients with beta thalassemia/hemoglobin E disease were measured. Two-dimensional echocardiography was employed to evaluate chamber size, ejection fraction and muscle fiber shortening. The seventeen patients who had a mean hemoglobin concentration of less than 7.7 g/dl were found to have significantly larger cardiac chambers and higher cardiac output than the patients with higher hemoglobin concentrations. A statistically significant difference in ejection fraction and per cent of fractional shortening of cardiac muscle fibers was not found. A comparison of subjects with ferritin concentrations above and below 1,500 micrograms/L showed no significant difference in chamber sizes, ejection fraction and in per cent fractional shortening. However, a comparison of 14 patients with transferrin saturation > or = 80 per cent with those less than 80 per cent showed a significant decrease in both ejection fraction and fiber fractional shortening in the more highly saturated subjects. By using stepwise multiple regression analysis, the hemoglobin level was shown to significantly determine cardiac enlargement, while ejection fraction and percentage fractional shortening were significantly associated with transferrin-iron saturation. Thus, anemia leads to chamber enlargement, while high transferrin iron saturation is associated with cardiac muscle dysfunction. The findings in the individual patient reflect the integration of these two effects.

Thyroid dysfunction in multi-transfused iron loaded thalassemia patients.

Seventy-two transfusion-dependent iron loaded thalassemia patients were investigated for thyroid dysfunction by estimating circulating thyroid hormones (T4 and T3) and basal thyroid stimulating hormone (TSH). They were also evaluated for their liver function (biochemically) and iron overload by estimating serum ferritin. Thyroid failure (hypothyroidism) was documented in 14 patients (19.4%). In all, 3 groups were seen, i.e. Group 1: Normal T4, T3, TSH (58 patients: 80.6%); Group 2: Compensated hypothyroidism characterized by normal T4, T3 and raised TSH (9 patients: 12.5%); Group 3: Decompensated hypothyroidism characterized by decreased T4 and increased TSH (5 patients: 6.9%). Interestingly, impaired thyroid function could not be correlated with age, amount of blood transfused, liver dysfunction or degree of iron overload. It is postulated that an inter-play between chronic hypoxia, liver dysfunction and iron overload may be responsible for the thyroid damage.