Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran

BACKGROUND: The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. METHODS: Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. RESULTS: Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 ± 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected. CONCLUSION: High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions

The relationship between some endometrial secretion cytokines and in vitro fertilization

Background: Endometrial secretion analysis is a non-invasive and promising method in evaluation of endometrial receptivity. Objective: The aim of the present study was to assess the relationship between the success rate of IVF procedures and some endometrial secretion cytokines, including interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein (MCP). Materials and Methods: In a prospective cohort study, 50 women selected for IVF met the study inclusion criteria. All the patients underwent endometrial secretion aspiration prior to embryo transfer. The level of IL-1β, TNF-α, IP-10 and MCP were analyzed by enzyme-linked immunosorbent assay method using special standard kits. To detect successful implantation and pregnancy patients underwent serum human chorionic gonadotropin measurements and ultrasound evaluation. Results: Five samples were excluded. Nine women (20%) had successful clinical pregnancies, which resulted in live birth. Other 36 women (80%) were classified as failed pregnancy. Comparison of cytokine levels showed lower concentrations of TNF-α, IP-10, and MCP in the group with successful clinical pregnancy compared to the group with failed pregnancy (p=0.007, 0.005 and 0.001, respectively). However, no significant difference was revealed in IL-1β levels between two groups (p=0.614). Conclusion: The current study suggested that lower concentrations of TNF-α, IP-10, and MCP in endometrial secretions might be associated with improved endometrial receptivity and IVF outcome. Regarding IL-1β, no statistically significant differences were seen between the groups with and without successful pregnancy

Genotype–Phenotype Correlation in X-Linked Alport Syndrome

Mutations in the COL4A5 gene cause X-linked Alport syndrome (XLAS). Understanding the correlation between clinical manifestations and the underlying mutations adds prognostic value to genetic testing, which is increasingly available. Our aim was to determine the association between genotype and phenotype in 681 affected male participants with XLAS from 175 US families. Hearing loss and ocular changes were present in 67 and 30% of participants, respectively. Average age of participants at onset of ESRD was 37 years for those with missense mutations, 28 years for those with splice-site mutations, and 25 years for those with truncating mutations (P < 0.0001). We demonstrated a strong relationship between mutation position and age at onset of ESRD, with younger age at onset of ESRD associated with mutations at the 5` end of the gene (hazard ratio 0.766 [95% confidence interval 0.694 to 0.846] per 1000 bp toward the 3` end; P < 0.0001). Affected participants with splice mutations or truncating mutations each had two-fold greater odds of developing eye problems than those with missense mutations; development of hearing impairment showed a similar trend. Hearing loss and ocular changes associated with mutations located closer to the 5` end of the gene. These strong genotype–phenotype correlations could potentially help in the evaluation and counseling of US families with XLAS