Individuals with SATB2-associated syndrome with and without autism have a recognizable metabolic profile and distinctive cellular energy metabolism alterations.

SATB2-associated syndrome (SAS) is a multisystemic disorder characterized by developmental delay often with concurrent autistic tendencies. This study aimed to characterize cellular metabolic pathways and energy metabolism from cells derived from individuals with SAS. The cellular production of NADH (nicotinamide adenine dinucleotide, reduced form) as determined by the Phenotype Mammalian MicroArrays was measured in lymphoblastoid cell lines derived from 11 subjects with a molecularly confirmed diagnosis of SAS and compared to a control population of 50 age-matched typically developing individuals. All patients were evaluated clinically by a multidisciplinary team. Eleven individuals (five in a screening cohort and six in the validation cohort, mean age 6.1 years) were recruited to the study. All individuals had developmental delay and the diagnosis of autism was previously established in five of them. Key metabolic findings included reduced NADH production in the presence of phosphorylated carbohydrates (with corresponding increased production in the presence of alternative carbon-based energy sources), increased response to certain hormones (β-estradiol in particular), and significantly reduced levels of NADH in wells containing tryptophan. The individual analysis revealed no particular differences among the SAS subjects based on molecular findings or phenotypic features. In conclusion, individuals with SAS have a common and recognizable metabolic profile. A lower capacity to utilize glucose as an energy substrate could be contributing to the neurodevelopment phenotype of SAS. The identified abnormalities offer previously unexplored insight into the potential pathophysiology of common SAS phenotypic features.