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 (ß-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.

Epilepsy and Electroencephalographic Abnormalities in SATB2-Associated Syndrome.

BACKGROUND: Seizures are an under-reported feature of the SATB2-associated syndrome phenotype. We describe the electroencephalographic findings and seizure semiology and treatment in a population of individuals with SATB2-associated syndrome. METHODS: We performed a retrospective review of 101 individuals with SATB2-associated syndrome who were reported to have had a previous electroencephalographic study to identify those who had at least one reported abnormal result. For completeness, a supplemental survey was distributed to the caregivers and input from the treating neurologist was obtained whenever possible. RESULTS: Forty-one subjects were identified as having at least one prior abnormal electroencephalography. Thirty-eight individuals (93%) had epileptiform discharges, 28 (74%) with central localization. Sleep stages were included as part of the electroencephalographies performed in 31 individuals (76%), and epileptiform activity was recorded during sleep in all instances (100%). Definite clinical seizures were diagnosed in 17 individuals (42%) with a mean age of onset of 3.2 years (four months to six years), and focal seizures were the most common type of seizure observed (42%). Six subjects with definite clinical seizures needed polytherapy (35%). Delayed myelination and/or abnormal white matter hyperintensities were seen on neuroimaging in 19 individuals (61%). CONCLUSIONS: Epileptiform abnormalities are commonly seen in individuals with SATB2-associated syndrome. A baseline electroencephalography that preferably includes sleep stages is recommended during the initial evaluation of all individuals with SATB2-associated syndrome, regardless of clinical suspicion of epilepsy.