The association of TMPRSS6 gene polymorphism with iron status in Egyptian children (a pilot study).

Several studies have shown association of single nucleotide polymorphisms (SNPs) of hepcidin regulatory pathways genes with impaired iron status. The most common is in the TMPRSS6 gene. In Africa, very few studies have been reported. We aimed to investigate the correlation between the common SNPs in the transmembrane protease, serine 6 (TMPRSS6) gene and iron indicators in a sample of Egyptian children for identifying the suitable candidate for iron supplementation.Patients and methods One hundred and sixty children aged 5-13 years were included & classified into iron deficient, iron deficient anemia and normal healthy controls. All were subjected to assessment of serum iron, serum ferritin, total iron binding capacity, complete blood count, reticulocyte count, serum soluble transferrin receptor and serum hepcidin. Molecular study of TMPRSS6 genotyping polymorphisms (rs4820268, rs855791 and rs11704654) were also evaluated.Results There was an association of iron deficiency with AG of rs855791 SNP, (P = 0.01). The minor allele frequency for included children were 0.43, 0.45 & 0.17 for rs4820268, rs855791 & rs11704654 respectively. Genotype GG of rs4820268 expressed the highest hepcidin gene expression fold, the lowest serum ferroportin & iron store compared to AA and AG genotypes (p = 0.05, p = 0.05, p = 0.03 respectively). GG of rs855791 had lower serum ferritin than AA (p = 0.04), lowest iron store & highest serum hepcidin compared to AA and AG genotypes (p = 0.04, p = 0.01 respectively). Children having CC of rs11704654 had lower level of hemoglobin, serum ferritin and serum hepcidin compared with CT genotype (p = 0.01, p = 0.01, p = 0.02) respectively.Conclusion Possible contribution of SNPs (rs855791, rs4820268 and rs11704654) to low iron status.

Navigating Hemostasis of Bleeding Among Children With ß-Thalassemia.

Bleeding phenotype is reported in ß-thalassemia patients. However, the underlying etiology remains elusive. We aimed to assess coagulation profile and the platelet aggregation in ß-thalassemia children with bleeding diathesis. Fifty ß-thalassemia children with a positive bleeding history were recruited. Bleeding phenotype was explored through full history taking and thorough clinical examination. Complete blood count, prothrombin time, international normalized ratio, and platelets aggregometry were performed for children with negative workup. Mucosal bleeding was manifest among most of our patients (96%). Two-third of patients had decreased aggregation with ristocetin (68%), adenine di-phosphate (64%), and arachidonic acid (64%). While half of the patients (48%) had deficient response to epinephrine. Collagen, ristocetin, and arachidonic acid induced aggregation were negatively correlated to frequency of blood transfusion (P=0.021, r=-0.325; P<0.001, r=-0.465; P=0.018, r=-0.333, respectively). Aggregation to collagen and epinephrine demonstrated a negative correlation with age (P=0.04, r=-0.287; P=0.03, r=-0.315). Deferiprone was associated with a deficient response to ristocetin and collagen when compared with deferasirox or no chelation (P=0.021 and 0.006, respectively). Impaired ristocetin response was linked to hydroxyurea (P=0.035). Platelets function defect should be considered in ß-thalassemia patients with bleeding symptoms.

Low Dose Iron Therapy in Children with Iron Deficiency: DNA Damage and Oxidant Stress Markers.

Conflicting data are available regarding oral iron therapy in iron deficiency (ID), iron deficiency anemia (IDA) and its relation to DNA damage, oxidative stress and antioxidant markers. Our aim was assessment of DNA damage, oxidative stress and anti-oxidant markers in children with ID and IDA before and after low dose iron therapy. The study was conducted in two stages, first stage was assessment of DNA damage using comet assay, malondialdehyde (MDA) and anti-oxidant enzymes levels (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) & total antioxidant capacity (TAC) in thirty-nine children with IDA, forty-five children with ID without anemia and sixty healthy controls. Second stage was assessment of previous markers together with hematological response following oral therapy with 10 mg/day ferric ammonium citrate for 8 weeks. Before treatment, there was no significant difference between the three groups regarding MDA, GPx, SOD, CAT and TAC. A significant increase was detected in the DNA damage in the 2 groups compared to control (p < 0.005). Following iron therapy, hematological parameters was improved together with a significant increase in GPx (P = 0.04), SOD (p = 0.002), TAC (P = 0.001) and non-significant reduction in DNA damage in IDA group. There was a significant increase in SOD (p = 0.001) & TAC (p = 0.001) and significant decrease in DNA damage (p = 0.001) in ID group. Low dose iron therapy could be sufficient to improve antioxidant status and DNA damage together with correction of hematologic indices.

Assessment of serum level of corticotropin-releasing factor in primary nocturnal enuresis.

INTRODUCTION: Primary nocturnal enuresis is one of the sleep related phenomena characterized by disruption in the relationship between arousal and urination. Corticotropin-releasing factor (CRF) is a neurohormone released from the paraventricular nucleus of the hypothalamus into the median eminence to elicit release of adrenocorticotrophin from the anterior pituitary. It may act to modulate autonomic function and behavior in concert with the endocrine effects. Conflicting animal studies about the role of CRF in micturition, either facilitating or inhibiting, have been raised. It was suggested to be a novel target for treatment of urinary disorders based on the finding that manipulation of CRF in the pontine micturition circuit could affect urodynamic function. AIM: The aim was to throw light on the possible role of CRF in primary monosymptomatic nocturnal enuresis by assessing its serum level. SUBJECTS AND METHODS: Twenty-nine children aged 8-14 years complaining of primary monosymptomatic nocturnal enuresis and 16 age- and sex-matched healthy children with good toilet control day and night were recruited to the study. History taking, clinical examination, and assessment of serum CRF levels in the morning and evening (9 a.m. and 9 p.m.) were carried out for all patients and controls. RESULTS AND DISCUSSION: A positive family history of enuresis was detected in 82.8% of enuretic patients. Serum levels of CRF (both morning and evening) were significantly lower in patients than in controls. Several animal studies suggested that CRF in descending projections from Barrington's nucleus to the lumbosacral parasympathetic neurons is inhibitory to micturition, which supports our results and the assumption that reduction of the evening serum CRF level could have a role in the occurrence of primary monosymptomatic nocturnal enuresis. No significant difference was found between morning and evening CRF serum levels in either cases or controls, which negates our assumption of having a rhythmic pattern of release (figure). No correlations with age were found. According to their history, all our enuretic patients were deep sleepers. Deep sleep and difficult arousal were found to have a major role in primary monosymptomatic nocturnal enuresis. It was proposed that CRF function may allow arousal to occur before micturition to facilitate preparative behaviors. A lower CRF level may explain deep-sleep pattern in children with enuresis. CONCLUSION: CRF was deficient in our enuretic children, which may draw attention to the possible pathophysiological implications in primary nocturnal enuresis (either at the level of loss of inhibitory effect on micturition or lack of arousal in response to bladder distension). Further proof studies are recommended.

Serum cystatin C is a poor biomarker for diagnosing acute kidney injury in critically-ill children.

BACKGROUND: Accurate diagnosis of acute kidney injury (AKI) is problematic especially in critically-ill patients in whom renal function is in an unsteady state. AIM: Our aim was to evaluate the role of serum (S.) cystatin C as an early biomarker of AKI in critically-ill children. SUBJECTS AND METHODS: S. creatinine and S. cystatin C were measured in 32 critically-ill children who were at risk for developing AKI. AKI was defined by both: Risk,-injury,-failure,-loss, and-endstage renal disease (RIFLE) classification and glomerular filtration rate (GFR) <80 ml/min/1.73 m(2). GFR was estimated by both Schwartz formula and S. cystatin C-based equation. RESULTS: S. cystatin C was not statistically higher in AKI patients compared with non-AKI by RIFLE classification (median 1.48 mg/l vs. 1.16 mg/l, P = 0.1) while S. creatinine was significantly higher (median 0.8 mg/dl vs. 0.4 mg/dl, P = 0.001). On estimating GFR by the two equations we found, a lag between rise of S. cystatin C and creatinine denoted by lower GFR by Schwartz formula in four patients, on other hand, six patients had elevated S. cystatin C with low GFR despite normal creatinine and GFR, denoting poor concordance between the two equations and the two markers. The ability of S. creatinine in predicting AKI was superior to S. cystatin with area under the curve (AUC) 0.95 with sensitivity and specificity (100% and 84.6%, respectively) using the RIFLE classification. The same findings were found when using Schwartz formula. CONCLUSION: S. cystatin C is a poor biomarker for diagnosing AKI in critically-ill children.

Anti-diuretic hormone and genetic study in primary nocturnal enuresis.

OBJECTIVE: To investigate whether primary nocturnal enuresis (PNE) is related to a disturbance in anti-diuretic hormone (ADH) secretion pattern at night which may be genetically inherited. SUBJECTS AND METHODS: This study included 121 children aged 6-18 years with PNE and 45 matched healthy children as controls. Enuretic children were subjected to genetic evaluation and cytogenetic assessment (n = 99). Assay of ADH levels (9-11 am & 9-11 pm) was performed for cases (n = 99) and controls. RESULTS: There was a positive family history in 82.4% (autosomal dominant in 35.4% and autosomal recessive in 64.6%). ADH morning and evening values were reversed in cases vs controls with significant difference in morning level. Reversal of circadian rhythm was present in 71.7% of cases and normal rhythm in 28.3% of them. Morning and evening ADH levels revealed significant difference between patients with reversed rhythm and those with normal one, and with controls. Mode of inheritance had no influence on hormonal level. Chromosomal abnormality was detected in 3 cases with reversed ADH rhythm, involving chromosome 22 in two of them. CONCLUSION: PNE could be attributed in part to reversed ADH circadian rhythm which may be linked to chromosome 22.

An SP1-binding site polymorphism in the COLIAI gene and osteoporosis in Egyptian patients with thalassemia major.

ß-Thalassemia major is an inherited blood disorder, which mainly affects the Mediterranean region. Osteoporosis represents an important cause of morbidity in ß-thalassemia major and its pathogenesis has not been completely clarified. Genetic factors play an important role in the pathogenesis of osteoporosis and several candidate gene polymorphisms have been implicated in the regulation of this process. A G→T polymorphism in the regulatory region of the collagen type I alpha 1 (COLIAI) gene at a recognition site for transcription factor Sp1 has been strongly associated with osteoporosis. The aim of the present study was to examine the distribution of COLIAI polymorphism and its relationship with bone mineral density (BMD) at the lumbar spine and femur in patients and controls. In this study, the G→T polymorphism was detected in 31 Egyptian ß-thalassemia major patients and 20 healthy controls and its possible association with BMD was investigated. Alleles S and s were detected by the presence of a G or T nucleotide, respectively, in a regulatory site of the COLIAI gene using polymerase chain reaction (PCR). A total of 80.6% of the ß-thalassemia patients were homozygous for G/G (SS) and 19.4% were heterozygotes for G/T (Ss) polymorphism. There was no ss genotype in our patients. In the control group, 70 and 30% had SS and Ss genotypes, respectively. There was no significant difference between Z-score of patients with SS and Ss at head of femur (P = 1) or at lumbar spine (P = 0.48). Conclusion Our results raise the possibility that genotyping at the Sp1 site could be of clinical value in identifying the thalassemic patients at risk of developing osteoporosis.