SummaryBackgroundRecently, vitamin D deficiency has been implicated as a potential environmental factor triggering some autoimmune disorders, including systemic lupus erythematosus (SLE)). In addition, patients with SLE, especially those with increased disease activity, were suggested to have decreased vitamin D level, suggesting that vitamin D might play a role in regulating autoantibody production.Material/MethodsTo assess 25 hydroxy vitamin D [25(OH)D] status in Egyptian patients with SLE and its relation to disease activity. Clinical evaluation and assay of serum 25(OH)D, total calcium, phosphorous, alkaline phosphatase (ALP) and parathyroid hormone (PTH) were done on 60 SLE patients in comparison to 60 matched-healthy subjects. Serum 25(OH)D levels <30 and 10 ng/ml were defined as vitamin D insufficiency and deficiency, respectively.ResultsSerum 25(OH)D was significantly lower in patients than in controls (26.33±12.05 vs. 42.66±9.20 respectively, p<0.0001), with 13.30% and 60% being deficient and insufficient, respectively. Serum 25(OH)D levels were lower with increased disease activity (p=0.03) and frequency of photosensitivity(p=0.02) and photoprotection (p=0.002). Systemic lupus erythematosus disease activity index (SLEDAI) score (OR: 2.72, 95% CI: 1.42–5.18, P=0.002), photosensitivity (OR: 3.6, 95% CI: 1.9–6.8, P<0.01) and photoprotection (OR: 6.7, 95% CI: 2.9–8.8, P<0.001) were significant predictors of 25(OH)D level among SLE cases.ConclusionsLow vitamin D status is prevalent in Egyptian SLE patients despite plentiful exposure to sunlight throughout the year, and its level is negatively correlated to disease activity. Future studies looking at a potential role of vitamin D in the pathophysiology and treatment of SLE are warranted.

BackgroundThe relationship between zinc (Zn) and growth hormone-insulin growth factor (GH-IGF) system and how Zn therapy stimulates growth in children has not been clearly defined in humans. Thus, we aimed to assess GH-IGF axis in short children with Zn deficiency and to investigate the effect of Zn supplementation on these parameters.MethodsFifty pre-pubertal Egyptian children with short stature and Zn deficiency were compared to 50 age-, sex-, and pubertal stage- matched controls. All subjects were subjected to history, auxological assessment and measurement of serum Zn, IGF-1, insulin growth factor binding protein-3 (IGFBP-3); and basal and stimulated GH before and 3 months after Zn supplementation (50 mg/day).ResultsAfter 3 months of Zn supplementation in Zn-deficient patients, there were significant increases in height standard deviation score (SDS, P = 0.033), serum Zn (P < 0.001), IGF-1 (P < 0.01), IGF-1 standard deviation score (SDS,P < 0.01) and IGFBP-3 (P = 0.042). Zn rose in all patients but reached normal ranges in 64 %, IGF-1 levels rose in 60 % but reached normal ranges in 40 % and IGFBP-3 levels rose in 40 % but reached reference ranges in 22 %. Growth velocity (GV) SDS did not differ between cases and controls (p = 0.15) but was higher in GH-deficient patients than non-deficient ones, both having Zn deficiency (p = 0.03).ConclusionSerum IGF-1 and IGFBP-3 levels were low in short children with Zn deficiency, and increased after Zn supplementation for 3 months but their levels were still lower than the normal reference ranges in most children; therefore, Zn supplementation may be necessary for longer periods.

BackgroundAutism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA) axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism.AimTo assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH) levels in autistic children and their relationship to disease characteristics.MethodsFifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated) and ACTH. In addition, electroencephalography (EEG) and intelligence quotient (IQ) assessment were done for all autistic children.ResultsSixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032) and stimulated cortisol (p = 0.04) and higher ACTH (p = 0.01) than controls. Childhood Autism Rating Scale (CARS) score correlated positively with ACTH (r = 0.71, p = 0.02) and negatively with each of basal (r = -0.64, p = 0.04) and stimulated cortisol (r = -0.88, p < 0.001). Hormonal profile did not differ in relation to EEG abnormalities, IQ and self- aggressive symptoms.ConclusionsThe observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

Background/Aims: The etiology of the hypoferremia of obesity is unclear. Hepcidin is the body's main regulator of systemic iron (Fe) and has been reported to be elevated in obese patients.Thus, we aimed to assess Fe status and serum hepcidin-25 levels and their relationship with body mass index (BMI) in obese Egyptian children and adolescents. Methods: Fifty obese children were compared to 50 age-, sex- and pubertal stage- matched controls. All subjects were subjected to history and anthropometric assessment and measurement of serum Fe, total iron binding capacity (TIBC), ferritin, transferrin saturation (TS), soluble transferrin receptor (sTfR) and hepcidin. Results: Fe, TS and TIBC were lower, while ferritin, sTfR and hepcidin-25 were higher in obese patients than controls. BMI standard deviation score (SDS) correlated negatively with Fe (r = -0.82, p < 0.01), TS (r = -0.79, p = 0.02) and TIBC (r = -0.69, p = 0.02), and positively with ferritin (r = +0.73, p < 0.001), sTfR (r = +0.80, p < 0.01) and hepcidin (r = +0.95, p < 0.001). Higher BMI SDS and hepcidin were risk factors for iron deficiency (ID). Conclusions: Hypoferremia and elevated hepcidin-25 are prevalent in obese children and correlated with BMI SDS.The connection between hepcidin and inflammation could explain the association of ID with obesity.

Hyperandrogenemia is prevalent in autistic patients and increases with autistic severity. Thus, androgen levels should be assessed in autistic patients with signs of early puberty. Further studies are warranted regarding trials of anti-androgen therapy in such patients.

Background: Homozygous loss-of-function mutations in the FOXE1 gene have been reported in several patients with partial or complete Bamforth-Lazarus syndrome: congenital hypothyroidism (CH) with thyroid dysgenesis (usually athyreosis), cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. Here, our objective was to evaluate potential functional consequences of a FOXE1 mutation in a patient with a similar clinical phenotype. Methods: FOXE1 was sequenced in eight patients with thyroid dysgenesis and cleft palate. Transient transfection was performed in HEK293 cells using the thyroglobulin (TG) and thyroid peroxidase (TPO) promoters in luciferase reporter plasmids to assess the functional impact of the FOXE1 mutations. Primary human thyrocytes transfected with wild type and mutant FOXE1 served to assess the impact of the mutation on endogenous TG and TPO expression. Results: We identified and characterized the function of a new homozygous FOXE1 missense mutation (p.R73S) in a boy with a typical phenotype (athyreosis, cleft palate, and partial choanal atresia). This new mutation located within the forkhead domain was inherited from the heterozygous healthy consanguineous parents. In vitro functional studies in HEK293 cells showed that this mutant gene enhanced the activity of the TG and TPO gene promoters (1.5-fold and 1.7-fold respectively vs. wild type FOXE1; p < 0.05), unlike the five mutations previously reported in Bamforth-Lazarus syndrome. The gain-of-function effect of the FOXE1-p.R73S mutant gene was confirmed by an increase in endogenous TG production in primary human thyrocytes. Conclusion: We identified a new homozygous FOXE1 mutation responsible for enhanced expression of the TG and TPO genes in a boy whose phenotype is similar to that reported previously in patients with loss-of-function FOXE1 mutations. This finding further delineates the role for FOXE1 in both thyroid and palate development, and shows that enhanced gene activity should be considered among the mechanisms underlying Bamforth-Lazarus syndrome.

Our study aimed to investigate: the prevalence of autoantibodies related to organ-specific disease; the prevalence of some autoimmune diseases (AID) in Egyptian Turner syndrome (TS) patients; and the association of autoimmunity with patients' karyotypes. Eighty TS patients were subjected to history, auxological assessment and measurement of antithyroid peroxidase antibody (ATPOAb), antithyroglobulin antibody (ATGAb), anti-tissue transglutaminase IgA antibodies (ATTIgAAb), anti-glutamic acid decarboxylase-65 antibodies (GAD-65-Ab) and anti-adrenal cortex antibodies (AACAb). Of the 80 TS patients, 54 (67.5%) were seropositive for one or more autoantibodies. Thirty-five percent were positive for ATPOAb, 15% for ATGAb, 12.5% for ATTIgAAb, 3.75% for Anti-GAD-65Ab and 1.25% for AACAb. There was a non-significant association between the 45,X karyotype and overall prevalence of autoantibodies (p=0.20), while IsoXq was associated with increased prevalence of ATPOAb (p<0.01), ATGAb (p=0.01) and anti-GAD-65Ab (p=0.02). Thus, female TS patients face a high prevalence of autoimmunity and associated AID.

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