Increased severity of fragile X spectrum disorders in the agricultural community of Ricaurte, Colombia

Abstract

Premutation carriers of the FMR1 gene (CGG repeats between 55 and 200) usually have normal intellectual abilities but approximately 20% are diagnosed with developmental problems or autism spectrum disorder. Additionally, close to 50% have psychiatric problems such as anxiety, ADHD and/or depression. The spectrum of fragile X disorders also includes Fragile‐X‐associated primary ovarian insufficiency (FXPOI) in female carriers and Fragile‐X‐associated tremor/ataxia syndrome (FXTAS) in older male and female carriers. We evaluated 25 premutation carriers in the rural community of Ricaurte Colombia and documented all behavioral problems, social deficits and clinical signs of FXPOI and FXTAS as well as reviewed the medical and obstetric history. We found an increased frequency and severity of symptoms of fragile X spectrum disorders, which might be related to the vulnerability of FMR1 premutation carriers to higher exposure to neurotoxic pesticides in this rural community.

Parental Reports on Early Autism Behaviors in Their Children with Fragile X Syndrome as a Function of Infant Feeding

“…The soy phytoestrogen daidzein is associated with increased seizure activity in mice [ 11 ], and the widely used herbicide glyphosate and its metabolite aminomethylphosphonic acid (AMPA) are found in soy-based infant formulas [ 52 ]. Increased severity and frequency of disease symptoms were found in FXS premutation carriers in the agricultural community of Ricaurte, Colombia and hypothesized to be associated with higher exposure to neurotoxic pesticides [ 53 ]. It remains to be determined if a bioactive component of soy or an altered amino acid profile contributes to an association with more severe autistic behaviors.…”

Fragile X syndrome in the largest world clustering. I. Genetic epidemiology and founder effect outline

“…For decades, it was assumed that the high prevalence of intellectual disability in Ricaurte relied upon environmental factors, among other myths, until we showed in 1990 that among the 1124 inhabitants of Ricaurte, 35 had FXS, for an estimated FXS prevalence of 1 in 38 men and 1 in 100 women, exceeding 100 times the prevalence reported in the literature worldwide (Saldarriaga et al, 2018;Saldarriaga et al, 2019). Using molecular diagnostic techniques (PCR and Southern Blot), we defined more precisely a premutation prevalence of 1 in 25 women and 1 in 85; a prevalence of full mutation of 1 in 46 women and 1 in 20 men; an FXTAS prevalence of 25% in women with premutation aged 50 years or older; 100% in men with permutation aged 50 years or older; and an FXPOI prevalence of 27.78% in women with premutation (Saldarriaga et al, 2018).…”

Case Report: Coexistence of Alzheimer-Type Neuropathology in Fragile X-Associated Tremor Ataxia Syndrome

“…Cognitive decline leading to dementia is seen in ∼50% of male patients with FXTAS (Seritan et al, 2016). Prior reports have introduced epigenetic/environmental risk factors related to an early presentation, greater severity of symptoms or faster progression of FXTAS including chronic use of addictive substances (Martinez-Cerdeno et al, 2015, Muzar et al, 2014, Muzar et al, 2015, anesthetics/general surgery (Ligsay et al, 2019), and exposure to environmental neurotoxins (Saldarriaga et al, 2019). Here we report an unusual case with a dramatic progression of cognitive decline associated with disinhibition in a patient with FXTAS and an APOE ε4 allele.…”