Impact of genotype on endocrinal complications in ß-thalassemia patients.

In ß-thalassemia, certain mutations cause a complete absence of ß-globin chain synthesis, termed ß0-thalassemia, while others may allow certain ß-globin production and are termed ß+- or ß++-thalassemia. The homozygous state results in severe anemia, which requires regular blood transfusion. By contrast, frequent blood transfusion can in turn lead to iron overload, which may result in several endocrinal complications. The present study aimed to investigate the impact of genotype on the development of endocrine complications in ß-thalassemia patients. A cross-sectional study was conducted on 100 thalassemia patients >10 years. A data abstraction form was designed to capture the appropriate information from the individual medical records, including full clinical, laboratory, transfusion and chelation data. The genotype of the patients was identified by the DNA sequencing technique. Growth retardation and hypogonadism were the most prominent endocrinal complications (70 and 67%, respectively) followed by hypothyroidism, diabetes mellitus and hypoparathyrodism (8, 8 and 7%, respectively). The most common mutations identified were IVS-1-110, IVS-1-1 and IVS-1-6 (63, 47 and 41%, respectively). Patients with the ß0ß0 genotype had a significantly higher prevalence of growth retardation, hypogonadism, hypothyroidism and hypoparathyrodism compared to those with the ß0ß+ and ß+ß+ genotypes (P<0.001, P<0.001, P<0.001 and P=0.037, respectively). Patients with the homozygous IVS-11-745 mutation had a significantly higher prevalence of diabetes (P=0.001). The underlying genetic defect in thalassemia patients is a contributing factor for the development of endocrinal complications, as patients with the more severe defects have a greater rate of iron loading through higher red cell consumption.

Effect of breastfeeding versus infant formula on iron status of infants with beta thalassemia major.

BACKGROUND: Thalassemia major or Cooley's anemia is the most severe form of beta thalassemia in which the complete lack of beta protein in the hemoglobin causes a life-threatening anemia requiring regular blood transfusions and extensive ongoing medical care. These extensive, lifelong blood transfusions lead to iron-overload that must be treated with chelation therapy to prevent early death from organ failure. We compared serum iron and ferritin levels amongst infants aged up to one year with beta thalassemia major according to their feeding types, including exclusively breastfed, exclusively formula fed and combined (both breast and formula) fed types. METHODS: Sixty out of 176 screened infants with transfusion dependant beta thalassemia major were recruited from the outpatient clinic of thalassemia at Zagazig University Hospital in Egypt, between 2007 and 2014. Patients were classified into three groups (20 patients per group) according to type of feeding. Group 1: exclusive breastfeeding, around 6-8 feeds per day; group 2: exclusive infant formula feeding, 120-150 ml of formula per kilogram of body weight per day divided into 6-8 feeds and group 3: combined breastfeeding and formula per day. RESULTS: Serum iron and ferritin levels were lower in group 1 compared to groups 2 and 3. The mean serum iron for group 1 was 73, 87 and 96 ug/dl at 6, 9 and 12 months respectively, while that for group 2 was 85, 99 and 112 ug/dl at 6, 9 and 12 months respectively and for group 3 was 78, 92 and 99 ug/dl at 6, 9 and 12 months respectively. The mean serum ferritin for group 1 was 283, 327 and 497 ng/ml at 6, 9 and 12 months respectively, while that for group 2 was 310, 389 and 591 ng/ml at 6, 9 and 12 months respectively and for group 3 was 291, 345 and 515 ng/ml at 6, 9 and 12 months respectively. The differences were not statistically significant. CONCLUSIONS: Breastfed infants with beta thalassemia major may accumulate less iron than infants fed iron fortified formula anticipating later onset of iron overload in the breastfed infants. Larger studies are needed to support these findings.

Clinico-epidemiology of neuroblastoma in north east Egypt: A 5-year multicenter study.

Neuroblastoma, an embryonal malignancy of the sympathetic nervous system, is the most frequent extracranial solid tumor The clinico-epidemiological features of neuroblastoma in infants and children were investigated between January 2005 and January 2010 at the Pediatric Oncology units of Mansoura, Zagazig, and Tanta University Children's Hospitals (Egypt). Of 142 cases of neuroblastoma, 10 were omitted from the study due to defective data. The median age of the patients was 30 months, with 75.8% aged ≥1 year and 24.2% aged <1 year at time of diagnosis. The male-to-female ratio was 1.06. Suprarenal glands were the most common primary tumor site (72.7%). The majority of the patients (76.7%) had stage IV disease. Favorable pathology was observed in 43.8% of patients, while 56.2% exhibited unfavorable pathology. The estimated survival rate of patients was 30.7±10.0%, and mean survival time was 24.2±5.2 months. The rate of mortality was 28.6% for patients aged <1 year, and 81.8% for those aged ≥1 year (P=0.005). For patients with favorable pathology, the rate of mortality was significantly lower (28.6%) compared with that of patients with unfavorable pathology (77.8%; P=0.049). Although the association between outcome and each of the primary tumor sites, children's oncology group risk and gender was statistically insignificant, a large effect size was identified between outcome and primary tumor site, as well as children's oncology group risk and a medium effect size was identified between outcome and gender. Additionally, an age of ≥1 year was associated with unfavorable pathology (P=0.024), stage IV disease (P=0.026) and a suprarenal primary tumor site (P=0.001).

Assessment of cognitive function in children with beta-thalassemia major: a cross-sectional study.

Multiple risk factors contribute to cognitive impairment in children with ß-thalassemia major. For a more refined understanding of this issue, we attempted to evaluate cognitive function in ß-thalassemia major patients and identify the relationship between possible cognitive dysfunction and the following: demography, transfusion and chelation characteristics, iron overload, and disease complications. We studied 100 ß-thalassemia major children and 100 healthy controls who matched well in terms of age, sex, and socioeconomic status. All participants underwent psychometric assessment using Wechsler Intelligence Scale for Children-Third Edition, Arabic version. The mean Full-Scale IQ and Performance IQ of patients were significantly lower than those of controls, whereas no significant difference was found for Verbal IQ. No significant relationship existed between IQ and any of the assessed parameters. We concluded that Performance IQ, not Verbal IQ, was significantly affected in ß-thalassemia major patients, but there was no clear association between IQ and any of the parameters.

Cardiac events and cardiac T2* in Egyptian children and young adults with beta-thalassemia major taking deferoxamine.

BACKGROUND AND OBJECTIVES: Cardiac events and death are not uncommon in adults with beta-thalassemia (b-TM) taking deferoxamine (DFO) monotherapy because of poor compliance and possibly the less effectiveness of DFO in controlling cardiac iron overload. We sought to assess compliance with DFO, the percentage of shift to other iron chelators, and the occurrence of cardiac siderosis, and cardiac events and death in b-TM patients on DFO monotherapy. DESIGN AND SETTING: Prospective, observational, 10-year follow-up of patients attending Ain Shams Thalassemia Unit, Cairo, Egypt. METHODS: For all b-TM patients aged 2-18 years attending the unit during January 1998 and taking DFO, we recorded all cardiac events (whether fatal or not) during January 2008. All patients still on DFO monotherapy and with a normal EKG and not showing symptoms or signs suggestive of heart failure (HF) were evaluated for cardiac siderosis by T2*. RESULTS: Of 412 patients, only 126 (31%) were still taking DFO monotherapy (only 43% of those were compliant), 136 were taking combined DFO and deferiprone (DFP), 72 were taking DFP and 32 were taking deferasirox (DFX). Twenty-one were lost to follow-up and 25 died (10 cardiac). Eight of ten cardiac deaths and 12 of 15 non-cardiac deaths were in the DFO monotherapy group. Those taking DFO monotherapy with no HF and left ventricular ejection fraction (LVEF) by T2* >56% had a median age of 19 years and 56% were males; cardiac T2* was less than 20 ms in 30 (22%), 10-20 ms in 20 (14.7%) and less than 10 ms in 10 (7.3%). LVEF ranged from 58%-76% (median 64%). Forty percent of T2* patients less than 10 ms were compliant with DFO. CONCLUSION: Fifty-eight percent of patients on DFO monotherapy were noncompliant, but even compliance did not prevent severe cardiac siderosis and most cardiac events (whether fatal or not) that occurred in the DFO monotherapy group.