Background: Autistic spectrum disorders (ASD) are neurodevelopmental disorders with unknown etiology characterized by disturbance in language, perception, and socialization. Oxidative phosphorylation (OXPHOS) is the enzyme system used to convert the food we eat to energy that can be used by the body (ATP, adenosine triphosphate). ATP is essential for normal brain function. Defects in OXPHOS may be the largest category of gene defects causing ASD and cause decreases in ATP production within cells. Patients with ASD are known to harbor abnormalities in OXPHOS as well as inherited mutations in OXPHOS genes.

Objective: Since OXPHOS defects can be observed in white blood cells, the objective of the study is to develop a screening test for ASD patients who harbor OXPHOS defects by quantitating ATP production within the mitochondria of their white blood cells.

Specific Aim and Impact: In order to detect decreases in ATP production, we plan to insert a gene into cultured white cells from fireflies that emits light when ATP is present. The white blood cells that are studied in cell culture were obtained during prior clinical evaluations. As more ATP is produced, more light is emitted from the cells. Patients with ASD due to mitochondrial disease would be predicted to generate less ATP and therefore emit less light from their white blood cells. This testing could be valuable for patients by decreasing the number of muscle biopsies performed for patient diagnosis.