Assessment of Essential and Toxic Element Levels in the Toenails of Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) has become a global public health concern, impacting the quality of life. The question of gene-environment interaction in the emergence of ASD remains a subject of ongoing debate, and exploring its pathophysiology is thoroughly related to metals as a risk factor. Therefore, this study aims to assess the levels of toxic (Al, Cd, Hg, and Pb) and essential (Cr, Mn, Fe, Ni, Cu, Zn, and Se) elements in toenail samples collected in children with ASD and neurotypical children, by ICP-MS. Parallelly, we will discuss the use of toenails as an exposure indicator. The study involved 208 children aged 3 to 14 from Marrakech, Morocco. One hundred two were diagnosed with ASD and 106 were neurotypical children. Significant statistical differences in the concentration of Cr, Mn, and Fe were documented between the two groups. Higher levels of Pb in toenails compared to reference values have been reported. No association was established between concentrations of elements and age. Spearman correlation coefficients revealed a significantly different pattern of mutual dependence for toxic and essential elements between the two groups. The strongest positive correlations were found in the neurotypical group (Fe-Mn (ρ = 0.750), and Se-Zn (ρ = 0.800)). These results provide additional, although inconclusive, evidence on the probable role of element disturbance in the pathogenesis of ASD. Further studies should be performed to explore other nutritional, cultural, sociodemographic, environmental, and methodological factors that may impact the levels of these elements in the nails and their possible correlation with the incidence of ASD.

Phenotype and molecular characterization of Wilson's disease in Morocco.

BACKGROUND AND STUDY AIMS: In Morocco the prevalence of Wilson disease (WD) and the spectrum of mutations are not known. The aim of the present study was to estimate the prevalence of WD in Morocco, to evaluate the phenotype among a large cohort of WD patients, and to characterize ATP7B variants in a subgroup of WD patients. PATIENTS AND METHODS: We collected data from 226 patients admitted to five university hospital centers in Morocco between 2008 and 2020. The diagnosis was based on clinical manifestations, function tests and biochemical parameters. The genotype was characterized in 18 families diagnosed at the University Hospital Center of Marrakesh, by next generation sequencing. RESULTS: The mean annual prevalence in Morocco was 3.88 per 100,000 and the allele frequency was 0.15 %. Among the 226 patients included (121 males and 105 females), 196 were referred for a hepatic or neurological involvement and 30 were asymptomatic. The mean age at diagnosis was 13 ± 5.1 years (range: 5 - 42 years). Consanguinity was found in 63.3 % of patients. The mean duration of illness was 2.8 ± 1.9 years. Kayser-Fleischer rings were found in 131 (67.9 %) of 193 patients. Among the 196 symptomatic patients, 141/159 (88.7 %) had low serum ceruloplasmin (<0.2 g/L) and a high 24-hours urinary copper (>100 µg/day) was found in 173/182 (95.1 %) patients. The initial treatment was D-penicillamine in 207 patients, zinc acetate in five, zinc sulfate in five, and nine patients were not treated; 60/207 (29 %) patients have stopped treatment. A total of 72 patients died; the mortality rate was 31.9 %. Eight different ATP7B variants were identified among the 18 patients studied, of which two were novel (p.Cys1104Arg and p.Gln1277Hisfs*52), and six previously published (p.Gln289Ter, p.Cys305Ter, p.Thr1232Pro, p.Lys1020Arg, p.Glu583ArgfsTer25 and c.51+4A>T). All informative patients were homozygous for the disease-causing mutation. CONCLUSION: In Morocco, a high prevalence due to consanguinity and a high mortality rate due to the difficulty of diagnosis and lack of treatment were observed in WD patients. NGS sequencing identified new ATP7B variants in WD patients from Morocco.

Hair Trace Elements and Mineral Content in Moroccan Children with Autism Spectrum Disorder: a Case-Control Study.

The prevalence of autism spectrum disorder (ASD) around the world continues to increase while the pathophysiology remains insufficiently elucidated. Genetics, environment, and epigenetic changes are often implicated. Abnormal level in trace elements and minerals is among environmental factors assumed to be involved. The purpose of this article is to assess hair concentrations of toxic and essential elements in children with ASD and children with neurotypical development in the city of Marrakech. Two hundred and twenty-seven children (107 with ASD and 120 controls) aged 3 to 14 years old were recruited. The results of analysis by ICP-MS showed a significant decrease in hair levels of copper, zinc, iron, and selenium (25%, 13%, 17%, 11%) of children with ASD. The most significantly reduced concentrations in children with ASD are that of manganese by 34%. Hair aluminum level was significantly elevated by 29% in ASD compared to controls. Multiple linear regression analysis revealed that copper, selenium, and iron content in hair were significantly inversely associated with ASD, similarly, hair aluminum content was significantly associated with ASD. Adjusted model for demographic parameters increased the predictive ability of the model, father's age was a significant predictor. In addition, ASD and gender were significant predictors of hair levels of aluminum, selenium, and manganese.These results support the hypothesis of the disparity of trace elements and minerals levels in children with ASD and highlight the potential interest of micronutrient supplementation in the eventual improvement of ASD symptoms. Future research should explore the pathophysiology of these micronutrient deficiencies.

Iron deficiency and cognitive impairment in children with low blood lead levels.

Background: The relationship between iron deficiency (ID) and children's neurocognitive functions has attracted the interest of the scientific community, particularly among those living at the lead-contaminated sites. Thus, the current paper aims at evaluating the association between ID and neurocognitive performance of school children living in a mining area (CMA) in comparison with a control group (CG). Methods: he study involves 90 school children aged from 6 to 10 years old. A survey was conducted to obtain information on the socio-economic and demographic status of the children. The students underwent cognitive test battery including the Bell Dam Test (BDT) and the Digit Span test (DST). Iron status (IS) was determined by serum iron, ferritin, transferrin, and blood count (CBC). Blood lead levels (BLLs) were measured by the Graphite Furnace Atomic Absorption Spectrophotometer (SAA-FG). Results: An ID was observed in 23.3 % of CMA, but it is not statistically different from the CG 21.7 % (p = 0.774). CMA group exhibited elevated BLLs (3.5 ± 1.21 µg/dL) when compared to the CG (2.31 ± 0.95 µg/dL), p = 0.006. Children's performance on the visual attention test (VA) was impaired in both groups. Working memory (WM) abilities were normal. In bivariate analysis, no difference was demonstrated in mean BLLs between the students who adopt the disorganized scanning strategy compared to the others whose method is organized for both CMA (t = - 0.508, p = 0.616) and CG (t = - 0.014, p = 0.989). Multivariate models did not reveal any association between IS and cognitive scores of children in the two groups (p > 005). Nevertheless, daily milk consumption was positively associated to VA skills among CMA. A negative influence of BLLs above the threshold value of 5 µg/dL was determined on children's WM skills. Conclusion: Our results suggest that low-level lead exposure did not influence children's visual attention scores but may adversely affect WM abilities if it reaches the threshold value of 5 µg/dL regardless of their IS.