Mutational analyses of mitochondrial ATP6 gene reveal a possible association with abnormal levels of lactic acid and ammonia in Bangladeshi children with autism spectrum disorder: A case-control study

Autism spectrum disorder (ASD) is a multifactorial and highly heterogeneous neurodevelopmental disorder. Mitochondrial dysfunction, caused by the genetic variations in the electron transport chain (ETC) complexes and marked by higher lactic acid and ammonia levels, can play a crucial role in the development of autism. This study focused on identifying genetic variants in the mitochondrial ATP6 gene of children with ASD and their association with autism disease outcome, disease severity, lactic acid and ammonia levels. Ninety children were recruited of which 53 were with autism and the remaining 37 were healthy controls. The ATP6 gene was amplified by PCR, purified, and sequenced by Sanger sequencing. In total forty-two genetic variants were identified within the gene. Among them 8886G > A and 8911 T > C were found to be associated with higher lactic acid levels and 8748C > T, 8886G > A, and 8964C > T were associated with higher ammonia levels after the adjustment with age, gender, and disease response. Additionally, all the synonymous variants were found to alter the relative synonymous codon usage (RSCU) values, potentially affecting the protein's structure and translation rate. Although there was no significant association between any ATP6 variants and disease outcomes, the variants associated with mitochondrial dysfunction as reflected by abnormal levels of lactic acid and ammonia may provide an improved understanding of the pathophysiology of ASD. Therefore they need to be explored further along with other components of the electron transport complex.