Hemoglobinopathies in the District of Antalya, Turkey

A screening program was conducted to ascertain the incidence of hemoglobinopathies in the district of Antalya, Turkey. The survey sample was selected from the household registration forms of health centers by systematic random sampling. Heparinized blood samples were collected from 1,616 subjects from 884 families.

The prevalence of p thalassemia traits with increased Hb A2 was 10.2%. This is higher than that found in previous studies performed in Antalya. The prevalence of abnormal hemoglobins (Hbs) was found to be 0.8%. Four subjects had Hb AS; five had Hb D-Los Angeles (B 121 [GH4] Glu-Gln); one had Hb Ube-2 (68 [E1] Asn-Asp), one had Hb P-Nilotic (fusion between B 22 and) and two had Hb D-like variants.     

Thrombocytosis Associated with Solid Tumors in Children

The association between thrombocytosis and malignant disease was first described by Levin and Conley in 1964¹ but its pathogenesis remains unknown. We have studied the platelet counts in 108 children with solid tumors presenting to this hospital over the last 5 years. Thrombocytosis was defined as a platelet count over 400 × 10⁹/L and was noted in 43 children (40%) at presentation; in the great majority of cases the thrombocytosis could not be ascribed to infection or hemorrhage. The platelet counts in relation to the six commonest diagnoses are shown in Figure 1. The association was particularly marked in the case of hepatic tumors, where 8 out of 10 patients had platelet counts at presentation above 400 × 10⁹/L with a mean of 647 ± 306 (SD) × 10⁹/L (range 294-1310). Thrombocytopenia (platelet count less than 150 × 10⁹/L) was noted in 5 children at presentation; 2 of these had morphological evidence of bone marrow infiltration.     

Detection of Early Cardiac Dysfunction in Patients with β-Thalassemia Major and Thalassemia Trait by Tissue Doppler Echocardiography

Cardiac complications are the leading cause of death in β-thalassemia major (TM) patients. The aim of this study was to investigate the impact of iron overload on ventricular functions using conventional and tissue Doppler imaging (TDI) in patients with TM and compare them with children with thalassemia trait (TT) and healthy controls. This prospective study includes 3 groups: group 1: 29 patients with β-TM; group 2: 28 patients with TT; group 3: 29 healthy controls. Peak late relaxation velocity determined by conventional echocardiography for the right ventricle was significantly higher and the E/A ratio for the right ventricle and left ventricle were significantly lower in TM patients than the other groups (P < .05). Peak late relaxation velocity determined by TDI for the left ventricle, interventricular septum, and right ventricle were significantly higher in TM patients than the TT subjects and controls (P < .001). The E/A ratio determined by TDI for the left ventricle, interventricular septum, and right ventricle were significantly lower in group 1 than the other 2 groups (P < .001). There was a negative correlation between the ferritin level and E/A ratio for the left ventricle, interventricular septum, and right ventricle using TDI (P < .05). Conventional echocardiographic techniques have failed to distinguish ventricular functions of asymptomatic patients with TM from the subjects with TT and from normal controls when global functions were examined. The present study indicates that TDI should be used for screening of TM and TT subjects’ cardiac functions.     

Prevalence of low bone mass among adolescents with nontransfusion‐dependent hemoglobin E/β‐thalassemia and its relationship with anemia severity

1 Background

Low bone mass is common among adolescents with transfusion‐dependent β‐thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion‐dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion‐dependent (NTD) β‐thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/β‐thalassemia.

2 Objective

To determine the prevalence of low bone mass among adolescents with NTD Hb E/β‐thalassemia and factors relating to low bone mass.

3 Methods

We investigated BMD of lumbar spine (L2–L4; BMDLS) and total body (BMDTB), as measured by dual‐energy X‐ray absorptiometry, in 22 adolescents (aged 13.2–20 years) with NTD Hb E/β‐thalassemia.

4 Results

Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z‐score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z‐score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z‐scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z‐scores adjusted for bone age.

5 Conclusion

We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/β‐thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long‐term bone health.     

448例β-地中海贫血的基因型与临床分析

目的 　探讨β -地中海贫血基因突变与临床病情的关系。方法 　应用PCR-RDB技术对 4 48例β -地中海贫血患儿进行基因诊断。结果 　检测出 1 2种基突变类型 ,有 2 4种基因组合形式。结论 　β。 纯合子及β° β°双重杂合子临床表现重 ,发病年龄、输血年龄均较早 ,β° β+双重杂合子表现为中间型或重型 ,发病年龄及输血年龄均较晚。     

The effect of deferasirox on endocrine complications in children with thalassemia

Abstract

Endocrine system dysfunctions are the significant complications of excessive iron overload in beta thalassemia patients. The aim of this study was to evaluate the long-term effect of chelation with deferasirox on endocrine complications. The study group consisted of children with beta thalassemia who had been evaluated for the growth and pubertal development, bone metabolism, thyroid/parathyroid functions, glucose metabolism dysfunctions in the department of pediatric hematology of Ankara D??kap? Child Health and Diseases Hematology Oncology Training And Research Hospital between 2009-2011 and reevaluated after deferasirox chelation therapy in 2018. Thirty-one transfusion dependent beta-thalassemia patients were enrolled for the study. Seventeen (54.8%) patients were male and the mean age was 16.9?±?3.8 (9-23) years. Splenectomy was performed in 11 patients (35.5%). In the initial evaluation, 26 patients (84%) received deferoxamine and/or deferiprone and five (17%) patients received deferasirox as a chelator; in the final evaluation all patients were receiving deferasirox. The mean duration of deferasirox treatment was 5.9?±?2.02?years (1-10?years). Of the 26 patients who had endocrine complications between 2009-2011, 18 were recovered. In the final evaluation, eight patients (25%) developed new endocrinopathies. The frequency of endocrine complications seen before the deferasirox treatment (83%) was higher than the frequency of complications while receiving deferasirox treatment (25.8%) (p?<?0,05). In this study, it was determined that both existing endocrine abnormalities were reduced and recent developed problems were less likely with long-term deferasirox treatment in thalassemia patients.     

Coagulation Contact Phase Factors and Inhibitors in β-Thalassemia Major Children

Selected hemostatic parameters of 23 children affected by β-thalassemia major were studied and compared to an age- and sex-matched group. Plasma prekallikrein level was reduced in all patients, splenectomized or not. In splenectomized patients, platelet count and in vitro platelet aggregability were significantly increased and Protein C was slightly increased. The activated partial thromboplastin time was prolonged and the normotest reduced. Finally, a reduction in the plasma levels of fibrinogen and of vitamin K-dependent proteins, including the antithrom-botic Protein C, was observed in nonsplenectomized patients. Our data indicate that the hemostatic system in patients with thalassemia major may be altered. The relationship between these laboratory changes and clinical manifestations remains to be established.     

The relation between left ventricular diastolic indices and serum ferritin in thalassemia major

Iron-induced heart failure is the primary cause of death in thalassemia major patients who receive continuous transfusions. Recent studies have suggested that diastolic function is impaired prior to systolic function in process of hemochromatosis, but they did not come to agreement on the first impaired diastolic index. Additionally, serum ferritin concentration is not a reliable indicator of body iron storage since it increases in any simple inflammation. Accordingly, the authors undertook this study to assess any association between left ventricular diastolic indices and serum ferritin in thalassemic patients with normal systolic function to estimate the true amount of body iron storage and correct it in earlier stages. Serum ferritin concentration and diastolic indices were measured in 29 patients with normal left ventricular systolic function. Linear regression test was used to find any association between hematological and cardiac factors. No significant association was found between diastolic indices and serum ferritin concentration. But the results were quite different in patients above and below 15 years of age; standardized coefficients (r) for peak of E and A were increased in patients above 15, and the significance was close to .05, unlike those of younger group. Although no correlation was found between serum ferritin and diastolic indices, the results were noteworthy in patients above 15. To appropriately judge this relation, the study must be continued with a bigger sample size and having patients' mean serum ferritin concentration during the 2 past years.     

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??Thalassemia is one of the most common and serious single-gene genetic diseases in the world. However??due to the lack of understanding of this disease by primary clinicians and parents of children??as well as the limitations of China’s economic development level??many children have not received timely diagnosis and formal treatment. It is of great significance to pay attention to the diagnosis and treatment of thalassemia in children??especially to improve the level of prenatal diagnosis and avoid the misdiagnosis of rare and poor gene mutations. It’s also important to perform proper treatment in order to enable the children to live longer and improve their life qualtiy.     

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??The classification of thalassemia is mainly based on the types of the defective synthesis of the globin chains of adult hemoglobin A and clinical features??the former mainly includes α??β??γ??δ??δβ??etc.??and α or β thalassemia is the most common form of thalassemia??the latter is classified as transfusion-dependent thalassemia and non-transfuion-dependent thalassemia in terms of long-term survival depending on blood transfusion. The diagnostic techniques include screening test and genetic test??the former diagnostic method is mainly based on the morphology of red blood cells and the physical and chemical properities??including routine analysis of blood??red blood cell morphology and hemoglobin electrophoresis??etc.??and the latter is mainly based on PCR technology??including gap-PCR??real-time PCR??gene chip and DNA screening??etc. This paper reviews the classification and laboratory diagnosis techniques in thalassemia??combining comprehesive screening method with technique of genetic diagnosis??which appropriately contributes to the diagnosis of thalassemia.     

Pseudotumor cerebri as a presenting symptom of hypoparathyroidism in a thalassemia patient

A 15-year-old patient with thalassemia major was admitted with restlessness, weakness and headache. On physical examination, signs of pseudotumor cerebri were evident. The serum calcium level was 1.35 mmol/1, and the serum phosphorous level 3.52 mmol/1. Subsequently, serum calcium, phosphorous 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) levels were measured in a group of 29 thalassemic patients. Low levels of 25 OHD were found in the older patients. The PTH, calcium and phosphorous levels were normal.     

Neurosecretory Dysfunction of Growth Hormone Secretion in Thalassemia Major

ABSTRACT. The growth retardation of children with thalassemia major is multifactorial. Along the endocrine axis of growth hormone (GH), serum somatomedin has been shown to be deficient and GH response to GH-relasing hormone impaired, while GH response to provocative stimuli is normal. We studied the spontaneous secretion of GH in seven patients with thalassemia major and growth retardation. Three of the patients were hypothyroid, and the other four were euthyroid. Spontaneous secretion of GH in all seven patients was subnormal: the number of pulses, the mean pulse amplitude, and the integrated concentration of GH were all lower than in 14 age- and sex-matched (10 pubertal and 4 prepubertal) control subjects. GH response to provocative stimuli was normal in the euthyroid patients. This pattern of response corresponds with the definition of neurosecretory dysfunction of GH secretion. It is concluded that the growth retardation of patients with thalassemia major is partly due to neurosecretory dysfunction of GH secretion.     

The Effect of HFE Polymorphisms on Cardiac Iron Overload in Patients with Beta-Thalassemia Major

Objective: We aimed to investigate the effect of human hemochromatosis protein (HFE) polymorphisms on cardiac iron overload in patients with beta-thalassemia major. Methods: Our study included 33 patients diagnosed with beta-thalassemia major who were treated with regular transfusions and chelation therapy. M-mode, tissue Doppler, and pulsed wave Doppler echocardiography were performed on all patients. T2* magnetic resonance imaging (MRI) scans were also performed. The HFE polymorphisms (H63D, C282Y, S65C, Q283P, E168Q, E168X, W169X, P160delC, Q127H, H63H, V59M, and V53M) were studied using polymerase chain reaction. Results: The H63D polymorphism was detected in six patients with beta-thalassemia major. Five patients were heterozygous for the H63D polymorphism, while one was homozygous. There were no other polymorphisms. There was no relationship between the HFE polymorphisms and either the serum ferritin levels or the T2-weighted MRI values (P > .05). Moreover, conventional echo and tissue Doppler echo findings were not correlated with the HFE polymorphisms. Pulmonary vein atrial reversal flow velocity, which is a manifestation of diastolic dysfunction measured with pulse wave echo, was higher in the patients with HFE polymorphisms (P = .036). Conclusions: The HFE polymorphisms had no effect on cardiac iron overload. However, pulmonary vein atrial reversal flow velocity measurements can provide important information for detecting diastolic dysfunction during cardiac follow-up of patients with HFE polymorphisms. Studies with more patients are needed to provide more information regarding this matter.     

Hemoglobin Hakkari: An autosomal dominant form of beta thalassemia with inclusion bodies arising from de novo mutation in exon 2 of beta globin gene

Certain β globin gene mutations produce a thalassemia major phenotype in the heterozygous state. While most such patients have thalassemia intermedia, we describe a young Guatemalan child with a de novo mutation in the β globin gene, codon 31 T → G (Hemoglobin Hakkari), who developed severe anemia at the age of 10 months and remains transfusion‐dependent. The substitution of B13 leucine with arginine in the β globin results in alteration of a critical heme contact point resulting in an extremely unstable variant hemoglobin and a clinical picture that is characterized by ineffective erythropoiesis and numerous intracytoplasmic inclusions within the erythrocyte precursors of the bone marrow. Pediatr Blood Cancer 2010;54:332–335. © 2009 Wiley‐Liss, Inc.