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Fetal Alcohol Spectrum Disorder (FASD) is a disorder caused by prenatal alcohol exposure which leads to neurobehavioral, psychological, and adaptive functioning impairments. It has been well established that executive functioning in this population is significantly impaired. Further, recent research has demonstrated that when compared to the general population, the FASD population has a greater prevalence of chronic health conditions including auto-immune disorders, immune conditions, cardiac disease, and glucose tolerance abnormalities. Executive functioning skills are important in managing chronic health conditions and research has demonstrated that they influence quality of life in multiple clinical populations. However, this relationship has not been examined in the FASD population, where executive functioning deficits are characteristic. Therefore, the purpose of the present study is to understand how executive functioning ability in young adults diagnosed with FASD relates to the presence of their chronic health condition(s) as well as their health related quality of life. To our knowledge, previous research has not investigated these variables in this population before and so this research is considered exploratory. Young adults (between age 15-29) diagnosed with FASD or FAS who were fluent in English were recruited to participate. A total of 12 participants were included in the analysis, with exactly half being diagnosed with at least one chronic health condition, and the majority of participants reporting some impairment in health related quality of life and in executive functioning. Non-parametric statistics (specifically Spearman Rank Correlations and the Mann-Whitney U test) were used to analyze the data. The findings suggest a relationship between the presence of chronic health conditions and health related quality of life, and between executive functioning and health related quality of life. A relationship was not observed between the presence of chronic health conditions and executive function.

Additional file 2. Analysis of PJL samples variants, This file includes the analytical description (with figures and tables) of PJL variants.

BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10). MATERIAL AND METHODS: Thirty five cases of MTO1 deficiency were identified and reviewed through international collaboration. The cases of two female siblings, who presented at 1 and 2years of life with seizures, global developmental delay, hypotonia, elevated lactate and complex I and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in detail. RESULTS: For the description of phenotypic features, the denominator varies as the literature was insufficient to allow for complete ascertainment of all data for the 35 cases. An extensive review of all known MTO1 deficiency cases revealed the most common features at presentation to be lactic acidosis (LA) (21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and 27/34 (79%) of patients with MTO1 deficiency, respectively; with global developmental delay/intellectual disability present in 28/29 (97%), feeding difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35 (34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19 different pathogenic MTO1 variants identified in these 35 cases: one splice-site, 3 frameshift and 15 missense variants. None have bi-allelic variants that completely inactivate MTO1; however, patients where one variant is truncating (i.e. frameshift) while the second one is a missense appear to have a more severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is not viable. A ketogenic diet may have exerted a favourable effect on seizures in 2/5 patients. CONCLUSION: MTO1 deficiency is lethal in some but not all cases, and a genotype-phenotype relation is suggested. Aside from lactic acidosis and cardiomyopathy, developmental delay and other phenotypic features affecting multiple organ systems are often present in these patients, suggesting a broader spectrum than hitherto reported. The diagnosis should be suspected on clinical features and the presence of markers of mitochondrial dysfunction in body fluids, especially low residual complex I, III and IV activity in muscle. Molecular confirmation is required and targeted genomic testing may be the most efficient approach. Although subjective clinical improvement was observed in a small number of patients on therapies such as ketogenic diet and dichloroacetate, no evidence-based effective therapy exists.