Iron metabolism in autism spectrum disorder; inference through single nucleotide polymorphisms in key iron metabolism genes.

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental problems with various genetic and environmental components. The ASD diagnosis is based on symptom expression without reliance on any biomarkers. The genetic contributions in ASD remain elusive. Various studies have linked ASD with iron. Since iron plays a crucial role in brain development, neurotransmitter synthesis, neuronal myelination and mitochondrial function, we hypothesized that iron dysregulation in the brain could play a role and contribute to the pathogenesis of ASD. In this study, we investigated single nucleotide polymorphisms in ASD in various iron metabolism genes, including the Transferrin Receptor (TFRC) gene (rs11915082), the Solute Carrier Family 11 Member 2 (SLC11A2) gene (rs1048230 and rs224589), the Solute Carrier Family 40 Member 1 (SLC40A1) gene (rs1439816), and hepcidin antimicrobial peptide (HAMP) gene (rs10421768). We recruited 48 patients with ASD and 88 matched non-ASD controls. Our results revealed a significant difference between ASD and controls in the G allele of the TFRC gene rs11915082, and in the C allele of the SLC40A1 gene rs1439816. In silico analysis demonstrated potential positive role of the indicated genetic variations in ASD development and pathogenesis. These results suggest that specific genetic variations in iron metabolism genes may represent part of early genetic markers for early diagnosis of ASD. A significant effect of SNPs, groups (ASD/control) as well as interaction between SNPs and groups was revealed. Follow-up post hoc tests showed a significant difference between the ASD and control groups in rs11915082 (TFRC gene) and rs1439816 (SLC40A1 gene). Backward conditional logistic regression using both the genotype and allele data showed similar ability in detecting ASD using allel model (Nagelkerke R2 = 0.350 p = 0.967; Variables: rs1439816, rs11915082) compared to genotype model (Nagelkerke R2 = 0.347, p = 0.430; Variables: rs1439816 G, rs1439816 C, rs10421768 A). ROC curve showed 54% sensitivity in detecting ASD compared to 47% for the genotype model. Both models differentiated controls with high accuracy; the allele model had a specificity of 91% compared to 92% for the genotype model. In conclusion, our findings suggest that specific genetic variations in iron metabolism may represent early biomarkers for a diagnosis of ASD. Further research is needed to correlate these markers with specific blood iron indicators and their contribution to brain development and behavior.

Reliability and validity of the Arabic version of the Early Onset Scoliosis 24 Items Questionnaire (EOSQ-24).

INTRODUCTION: Early Onset Scoliosis (EOS) is a complex pathology that covers a variety of etiologies, with onset before the age of 10 years. Surgical treatment of EOS should have the objectives of fulfilling maximum pulmonary function, spine length, with minimal hospitalizations, complications, and family burden. Radiographic parameters are an important standard in assessing treatment outcomes. However, the Early Onset Scoliosis Questionnaire-24 (EOSQ-24) was developed to measure the wider dimensions of outcomes involving the quality of life of patients and caregivers post-treatment. The aim of this study was to evaluate the validity and reliability of culturally adapted Arabic version of the EOSQ-24. METHODS: Translation and cross-cultural adaptation, based on published guidelines, were performed on the original English EOSQ-24 by a committee. The Arabic version of EOSQ-24 was applied to the caregivers of all 58 EOS patients who were treated surgically after signing a consent form. Reliability was assessed using Cronbach's α and item-total statistics for the whole questionnaire initially and for the each domain separately. Data quality was assessed by mean, median, percentage of missing data, ceiling and floor effects. Discriminative validity was examined using non parametric tests. RESULTS: The response for all items was excellent with only 1.7% (0-1) of responses missing. The floor effect ranged from 0% to 36.2% of patients and the ceiling effect ranged from 0 to 46.6%. Cronbach's α test reliability was found excellent (0.919), as was the internal consistency of all domains, with Cronbach α ranging from 0.903 to 0.918. Corrected item-total correlations were good for all domains (>0.3). Only one item (Question 21) showed low corrected item-total correlations (r = 0.222). However, Cronbach's α did not increase significantly when this item was deleted (0.920). CONCLUSION: The first adapted Arabic version of EOSQ-24 is found to have good validity and reliability, and it can be used to assess children in Arab societies with EOS.

Serum 25-hydroxyvitamin D and bone turnover markers in Palestinian postmenopausal osteoporosis and normal women.

This study evaluated the association of vitamin D and bone markers with the development osteoporosis in Palestinian postmenopausal women. Even though vitamin D deficiency was very high for the recruited subjects, it was not associated with osteoporosis except for bones of the hip. Age and obesity were the strongest determining factors of the disease. PURPOSE: The purpose of this study was to investigate the association of bone mineral density (BMD) with serum vitamin D levels, parathyroid hormone (PTH), calcium, obesity, and bone turnover markers in Palestinian postmenopausal women. METHODS: Three hundred eighty-two postmenopausal women (≥45 years) were recruited from various women clinics for BMD assessment (131 women had osteoporosis and 251 were normal and served as controls). Blood samples were obtained for serum calcium, PTH, 25(OH)D, bone formation (N-terminal propeptide (PINP)), and bone resorption (serum C-terminal telopeptide of type I collagen (CTX1)) markers. RESULTS: Women with osteoporosis had statistically significant lower mean weight, height, body mass index (BMI), and serum calcium (p < 0.05) compared to controls. No significant differences were detected between the mean values of bone turnover markers (CTX and PINP), 25(OH)D, and PTH of the two groups. Women with vitamin D deficiency (severe and insufficiency) represented 85.9% of the study subjects. Multiple and logistic regression showed that age and BMI significantly affected BMD and vitamin D had a significant association with BMD only at the lumbar spine. BMI was positively correlated with BMD and PTH but negatively correlated with vitamin D. Logistic regression showed that the odds ratio (OR) for having osteoporosis decreased with increasing BMI (overweight OR = 0.11, p = 0.053; obese OR = 0.05, p = 0.007). CONCLUSIONS: There was no direct correlation between BMD and PTH, bone turnover markers, and vitamin D except at the lumbar spine. A negative correlation between BMD and age and a positive correlation with BMI were observed. The protective effect of obesity on osteoporosis was complicated by the effect of obesity on vitamin D and PTH.

Total Antioxidant Status in Type 2 Diabetic Patients in Palestine.

The objective of this study was to compare the level of total antioxidant status (TAS) in type 2 diabetic and normal Palestinian subjects as well as the major factors influencing TAS levels. A sample of convenience composed of 212 type 2 diabetic and 208 normal subjects above the age of 40 were recruited. Only 9.8% of the subjects had normal body mass index (BMI) levels (<25), 29% were overweight (≥25 to <30), and 61.2% were obese (≥30). The mean levels of TAS were significantly higher in diabetic compared to control subjects (2.18 versus 1.84 mM Trolox, P = 0.001) and in hypertensive subjects compared to subjects with normal blood pressure (BP). Mean TAS levels were higher in obese compared to nonobese subjects (2.12 versus 1.85 mM Trolox, P = 0.001). Mean TAS levels were similarly higher in subjects with high fasting plasma glucose (FPG) compared to normal FPG (2.19 versus 1.90 mM Trolox) and high HbA1c (≥6.5%) compared to HbA1c < 6.5% (2.14 versus 1.91 mM Trolox). Multivariate analysis revealed that only diabetic status (P = 0.032) and the level of education (P = 0.036) were significantly associated with TAS. In conclusion diabetic patients had 18.5% increase in TAS levels compared to control subjects.

Epidemiology of visceral leishmaniasis in the Jenin District, West Bank: 1989-1998.

Fifty patients from rural areas in the Jenin district of the West Bank, Palestinian Authority, were diagnosed with visceral leishmaniasis (VL) between 1989 and 1998. Forty-nine (98%) were younger than 6 years old, the youngest being 9 months. The yearly incident rate of VL in the Jenin district was highest in 1994 (11.8/100,000) and decreased to 1.5/100,000 in 1998; a mortality rate of 4% was recorded. Seventeen (5.5%) of 308 dogs from the Jenin and Ramallah districts of the West Bank were seropositive by enzyme-linked immunosorbent assay in a survey of canine leishmaniasis. Although all the leishmanial strains cultured from humans and dogs were identified as Leishmania infantum by a species-specific polymerase chain reaction, further genetic analysis by restriction fragment length polymorphism of kinetoplast DNA revealed patterns of polymorphism within isolates. The findings indicate that an active focus of potentially fatal VL exits in the Jenin district of the West Bank and that the parasite, vector, and reservoir host are found in this area. The epidemiology of VL in that vicinity follows the pattern of a predominantly infantile disease traditionally found in Middle Eastern countries, without a considerable involvement of immunocompromised adults infected with HIV virus as reported in other regions.

Palestinian infantile visceral leishmaniasis caused by a genetic variant of Leishmania infantum belonging to a new zymodeme.

The parasites causing a Palestinian case of infantile visceral leishmaniasis (IVL) and those from four dogs from the Jenin District were identified serologically, biochemically and molecular biologically as Leishmania infantum, showing dogs act as a reservoir. The strain from the human case was distinct because of its unique 200-bp kDNA-polymerase chain reaction (PCR) component in its restriction fragment length polymorphism (RFLP) profile after digestion with the endonuclease RsaI, and by the electrophoretic mobility of its malate dehydrogenase (MDH(140)), designating it the reference strain of a new zymodeme of L. infantum, MON-281.