Objectives: To determine the relationship of both physical and behavioral phenotype to plasma and cerebral spinal fluid (CSF) sterol levels in individuals with SLOS.
Methods: Autism features, cognitive abilities, adaptive skills, and anatomical severity in 23 individuals with mild to moderate SLOS were correlated with plasma and CSF sterols.
Results: In SLOS, 56% had autism and 70% had ASD. Regression analyses with sterol levels and the scores of Autism Diagnostic Interview-Revised, IQ, adaptive behavior, and anatomical severity demonstrated that plasma and CSF 7DHC levels were the most significant correlates of social and nonverbal autistic symptom characteristics and that sterol ratios (7DHC+8DHC/ total sterols) were the most significant correlates of anatomical severity.
Conclusions: Using clinical assessment tools and metabolomic studies, we have been able to distinguish distinct neurobehavioral phenotypes among young persons with SLOS, and determined that ASD related behaviors in SLOS may be a functional consequence of the abnormal biochemistry in the brain and specifically due to the accumulation of 7DHC. Thus, in SLOS and non-SLOS hypocholesterolemic ASD, autistic symptoms may be potentially amendable to therapeutic interventions that increase cholesterol and reduce 7DHC levels. A study is being performed with AGRE multiplex non-SLOS hypocholesterolemic individuals to determine if there is a distinct physical and behavioral phenotype that represents an etiologically independent subgroup (endophenotype). In a community sample of mostly simplex families, a study is being performed to behaviorally characterize the hypocholesterolemic individuals and determine if cholesterol supplementation is safe and helpful for ASD-related behaviors.