RESUMO
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.
RESUMO
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.