HAMDY, M. O. N. A., N. Salama, G. Maher, and A. Elrefaee, "Vitamin D and Nonskeletal Complications among Egyptian Sickle Cell Disease Patients.", Advances in hematology, vol. 2018, pp. 3867283, 2018. AbstractWebsite

Lower levels of vitamin D have been documented in many patients with sickle cell disease (SCD), but data are still inconclusive regarding the association between vitamin D deficiency (VDD) and the occurrence or the severity of various SCD complications. Our study aimed to detect the prevalence of vitamin D deficiency among Egyptian patients with SCD and to associate it with the clinical course of the disease. We measured the level of 25-hydroxy vitamin D in 140 children (age from 4.3 to 15.5years), 80 patients with SCD and 60 controls using enzyme-linked immunosorbent assay. Vitamin D was deficient in 60% of SCD compared to 26.7% of controls. Severe VDD was significantly higher in SCD patients than controls. Patients were divided into 2 groups; Normal group (32 patients) and Deficient group (48 patients). There were statistically significant differences between the 2 groups regarding their age, height percentile, the presence of clinical jaundice, and osseous changes (P values 0.043, 0.024, 0.001, and 0.015, respectively). Hemoglobin and hematocrit values were significantly lower in Deficient group (P values 0.022 and 0.004, respectively) while the levels of aspartate aminotransferase, lactate dehydrogenase, and total and indirect bilirubin were significantly higher in the same group (P values 0.006, 0.001, 0.038, and 0.016, respectively). The frequency of blood transfusions, hospitalization, and vasoocclusive crisis previous year as well as the history of bone fracture and recurrent infections proved to be significantly higher in Deficient group. These findings suggest that VDD may play a role in the pathogenesis of hemolysis and other complication of SCD. Vitamin D monitoring and supplementation in patients with SCD should be implemented as a standard of care to potentially improve health outcomes in these affected patients.

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Mokhtara, D. A., M. M. Hamdyb, and A. M. Badr, "Frequency of human hemochromatosis (HFE) gene mutations in Egyptians with b-thalassemia", The Egyptian Society of Haematology, vol. 38, pp. 36-40, 2013. Abstractejhv38n1-print-final-7.pdf

Background Hereditary hemochromatosis is a disorder of
iron metabolism characterized by increased iron intake and
progressive storage and is related to mutations in the
HFE gene. Two point mutations have been described and
are referred to as H63D and C282Y. On the other hand, iron
overload is a well-documented complication in thalassemia
syndromes. Interactions between thalassemia and
hemochromatosis may further increase iron overload. This
work aimed at studying the frequency of the H63D
and C282Y mutations of the HFE gene in an Egyptian
population with b-thalassemia (thalassemia major,
intermedia, and minor) by comparing it with normal
individuals without hemoglobinopathies.
Participants and methods This study included 86
patients with b-thalassemia; 40 of these patients had
b-thalassemia major and intermedia and the other 46
patients had b-thalassemia minor (carriers). In addition,
70 individuals were included in the study and served as
controls. All the populations studied were screened for
H63D and C282Y mutations of the HFE gene using
the PCR-restriction fragment length polymorphism
(PCR-RFLP) method.
Results The allelic frequencies found for H63D and C282Y
mutations in this study were 18.6 and 0%, respectively,
among the total alleles of individuals with b-thalassemia
and 12.8 and 1.4% among controls without

Mokhtara, D. A., M. M. Hamdyb, and A. M. Badr, "Frequency of human hemochromatosis (HFE) gene mutations in Egyptians with b-thalassemia", The Egyptian Society of Haematology, vol. 38, pp. 36-40, 2013. Abstractejhv38n1-print-final-7.pdf

Background Hereditary hemochromatosis is a disorder of
iron metabolism characterized by increased iron intake and
progressive storage and is related to mutations in the
HFE gene. Two point mutations have been described and
are referred to as H63D and C282Y. On the other hand, iron
overload is a well-documented complication in thalassemia
syndromes. Interactions between thalassemia and
hemochromatosis may further increase iron overload. This
work aimed at studying the frequency of the H63D
and C282Y mutations of the HFE gene in an Egyptian
population with b-thalassemia (thalassemia major,
intermedia, and minor) by comparing it with normal
individuals without hemoglobinopathies.
Participants and methods This study included 86
patients with b-thalassemia; 40 of these patients had
b-thalassemia major and intermedia and the other 46
patients had b-thalassemia minor (carriers). In addition,
70 individuals were included in the study and served as
controls. All the populations studied were screened for
H63D and C282Y mutations of the HFE gene using
the PCR-restriction fragment length polymorphism
(PCR-RFLP) method.
Results The allelic frequencies found for H63D and C282Y
mutations in this study were 18.6 and 0%, respectively,
among the total alleles of individuals with b-thalassemia
and 12.8 and 1.4% among controls without

El-Beshlawy, A., A. El-Shekha, M. Momtaz, F. Said, M. HAMDY, O. Osman, S. Meshaal, T. Gafaar, and M. Petrou, "Prenatal diagnosis for thalassaemia in Egypt: what changed parents' attitude?", Prenatal diagnosis, vol. 32, issue 8, pp. 777-82, 2012 Aug. Abstract

OBJECTIVES: To present the current status of the prenatal diagnosis services and results from the largest thalassaemia center in Egypt treating 3000 patients. Traditionally, prenatal diagnosis has not been successful in reducing the births of affected children in Egypt, because the majority of women undergoing prenatal diagnosis continued to have affected pregnancies.

METHODS: Seventy-one pregnant mothers at risk for β-thalassaemia underwent prenatal diagnosis by chorionic villus sampling (n=57) or amniocentesis (n=14) between 11 to 14 weeks of gestation. Molecular characterization of fetal DNA by reverse dot blot hybridization and polymerase chain reaction-amplification refractory mutation system techniques was conducted in all cases.

RESULTS: Twenty-four women (33.8%) were found to have affected fetuses; 100% of these women opted to terminate the pregnancy. The change in attitude towards termination of pregnancy was related to in-depth counseling of the religious aspects towards prenatal diagnosis and termination of pregnancy. Forty-eight women (66.2%) with normal or carrier fetuses for β-thal requested human leukocyte antigen typing of the fetal material to determine if the fetus was a human leukocyte antigen match for their existing thalassaemic siblings.

CONCLUSION: This study demonstrates that prenatal diagnosis is feasible and acceptable in Egypt, a Muslim country, provided an in-depth discussion, which also addresses the religious considerations of prevention, is held with the couples.

Maha M. Eida, Sami A. Temtamyb, Engy S. Solimana, Marwa I. Shehaba, Sami H. Abd Alazizd, and D. B. H. and, "Evaluation of the in-vitro protective effect of plant extract (astaxanthin) on chromosomal breakage in Fanconi anemia cell culture", Middle East Journal of Medical Genetics, vol. 2, pp. 45–49, 2013. Abstractevaluation_of_the_in_vitro_protective_effect_of.2.pdf

Background
Fanconi anemia (FA) is an inherited bone marrow failure syndrome associated with
congenital abnormalities and hypersensitivity to DNA cross-linking agents. The high
frequency of chromosomal breaks in FA lymphocytes has been related to the increased
oxidative damage shown by these cells. Reactive oxygen species (ROS) are derived
from the metabolism of molecular oxygen. It is now assumed that ROS are involved
both in the initiation and in the progression of cancer. Antioxidants have the ability
to transform ROS into stable and harmless compounds. Astaxanthin is a natural
source of antioxidant; its effect might protect cells from oxidative damage. Its
antioxidant activity is far higher than that of vitamin E.
Aim of work
This study was designed to compare between the antioxidant effect of both
astaxanthin and vitamin E as measured by their ability to reduce the frequency
of induced chromosomal breakage in patients with FA.
Participants and methods
The current study included 15 patients with FA, nine females and six males, ranging
in age from 4 to 21 years. The diagnosis of FA was confirmed by induction of
chromosomal breakage by diepoxybutane. Astaxanthin and vitamin E were added at
the start of the peripheral blood lymphocyte cultures to provide the possibility to
improve the pro-oxidant state of the cells; then caffeine was added during the last
6 h of culture to induce chromosomal breakage.
Results and conclusion
The level of breakage was markedly reduced using astaxanthin and vitamin E; however,
there was no significant difference between the effects of both substances.
Astaxanthin was found in a wide diversity of natural sources; also, it is 10 times more
potent than vitamin A and much safer than vitamin E. Our study is the first to
investigate the effect of astaxanthin on chromosomal breakage in vitro. We conclude
that the administration could be beneficial for patients with FA to improve their
hematopoietic state.
Keywords:
antioxidant, astaxanthin, fanconi anemia, reduction of chromosomal breakage, vitamin E

El-Shanshory, M., A. Hagag, S. Shebl, I. Badria, A. Abd Elhameed, E. Abd El-Bar, Y. Al-Tonbary, A. Mansour, H. Hassab, M. HAMDY, et al., "Spectrum of Beta Globin Gene Mutations in Egyptian Children with β-Thalassemia.", Mediterranean journal of hematology and infectious diseases, vol. 6, issue 1, pp. e2014071, 2014. Abstract

BACKGROUND: The molecular defects resulting in a β-thalassemia phenotype, in the Egyptian population, show a clear heterogenic mutations pattern. PCR-based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of β-thalassemia is necessary for carrier screening, genetic counseling, and to offer prenatal diagnosis.

THE AIM OF THE WORK: was to evaluate the different β-globin gene mutations in two hundred β-thalassemic Egyptian children.

SUBJECTS AND METHODS: This study was carried out on two hundred β-thalassemic Egyptian children covering most Egyptian Governorates including 158 (79%) children with thalassemia major (TM) and 42 (21%) children with thalassemia intermedia(TI). All patients were subjected to meticulous history taking, clinical examination, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of the β-globin gene to detect the frequency of different mutations.

RESULTS: The most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A) 24%, IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon "Cd"39(C> T) 4%, -87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (-AA), Cd29(-G), Cd5 (-CT), Cd6(-A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G> C), Cd 28 (-C), Cap+1(A>C), -88(C>A), all of these rare mutations were present in 1%. There was a considerable variation in phenotypic severity among patients resulting from the interaction of different β(∘) and β+mutations. Furthermore, no genotype-phenotype association was found both among the cases with thalassemia major and the cases with thalassemia intermedia.

CONCLUSION: Direct DNA sequencing provides insights for the frequency of different mutations in patients with β-thalassemia including rare and/or unknown ones. The most common mutations in Egyptian children with beta thalassemia were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A)24%, IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%.

El-Beshlawy, A., L. Ragab, A. Abdelfattah, I. Y. Ibrahim, M. O. N. A. HAMDY, A. Makhlouf, E. Aoun, V. Hoffbrand, and A. Taher, "Improvement of cardiac function in thalassemia major treated with L-carnitine.", Acta haematologica, vol. 111, issue 3, pp. 143-8, 2004. Abstract

INTRODUCTION: Heart disease secondary to chronic anemia and hemosiderosis remains the major cause of morbidity and mortality in thalassemic patients. Chronic anemia and the tissue hypoxia it induces impair free fatty acid oxidation and ATP production in myocardial cells. The use of L-carnitine, a butyric acid derivative, may help overcome some of these defects.

OBJECTIVE: To investigate the effect of L-carnitine therapy on cardiac function in thalassemia major patients.

MATERIALS AND METHODS: Cardiac function was evaluated in 30 patients attending our clinic. The mean (+/-SD) age was 15.87 +/- 3.19 years. The studies we performed included echocardiography, Doppler and multigated equilibrium radionuclide angiography (MUGA). Systolic and diastolic function was evaluated before starting L-carnitine treatment and after 6 months of oral L-carnitine (50 mg/kg/day).

RESULTS: Echocardiography studies revealed no significant changes in systolic and diastolic function after L-carnitine therapy (p > 0.05). Analysis of the data taken by MUGA performed in 20 of the patients, however, showed a significant improvement of diastolic function after 6 months of L-carnitine therapy. The mean peak filling rate (end-diastolic volume/s) increased from 3.15 +/- 1.06 to 3.61 +/- 1.68 (p < 0.03). The time to peak (during filling) decreased significantly from 143.45 +/- 42.04 to 117.70 +/- 24.40 s (p < 0.02). Systolic function showed a significant increase in the left ventricular ejection fraction from 58.25 +/- 9.92 to 63.95 +/- 10.11% (p = 0.0001).

CONCLUSION: L-carnitine may be an effective drug for improving the cardiac status of thalassemic patients. MUGA is the most accurate technique of those used here for assessing left ventricular function in these patients.

El-Beshlawy, A., R. El Accaoui, M. Abd El-Sattar, M. H. Gamal El-Deen, I. Youssry, N. Shaheen, M. O. N. A. HAMDY, M. El-Ghamrawy, and A. Taher, "Effect of L-carnitine on the physical fitness of thalassemic patients.", Annals of hematology, vol. 86, issue 1, pp. 31-4, 2007 Jan. Abstract

Poor physical fitness is a common problem among thalassemic patients. L-Carnitine plays an essential role in fatty acid beta-oxidation, a process especially important in the organs that preferentially use fatty acid as a source of energy such as the myocardium and the skeletal muscles. The main objective of this study is to assess the effect of the administration of oral L-carnitine on exercise tolerance and physical fitness in patients with thalassemia major. Thirty patients followed up at the New Cairo University Children Hospital were included in this study. Clinical, laboratory, and cardiopulmonary exercise testing were performed before and after 6 months of oral L-carnitine therapy (50 mg/kg/day). The oxygen consumption, cardiac output, and oxygen pulse at maximal exercise significantly increased after L-carnitine therapy (p<0.001, p=0.002 and p<0.001, respectively). However, there was no significant change in minute ventilation and ventilatory equivalent of carbon dioxide (p=0.07 and p=0.06, respectively). A weak but positive correlation between the age of the patients and the degree of improvement in exercise parameters was noted. There was also significant increase in the blood transfusion intervals after L-carnitine administration (p=0.008). However, there was no significant change in hemoglobin concentration (p=0.4). L-Carnitine seems to be a safe and effective adjunctive therapeutic approach in thalassemic patients. It improves their cardiac performance and physical fitness. The younger the patients are, the higher is the degree of improvement in their exercise parameters.