Early Diagnostic Differences Between Children Diagnosed with Autism Spectrum Disorders (ASD) and Children with Comorbid ASD and Mitochondrial Disease

Background:  The frequency of mitochondrial defects in ASD are not known, but individuals with oxidative phosphorylation (OXPHOS) defects appear to be at greater risk for symptoms associated with ASD compared to individuals with typical mitochondrial functioning. Mitochondrial disease exacerbated by fever appears to contribute to regression observed in the early development of children with ASD (Schoffner et al., 2010). Little is known about the early diagnostic similarities between children on the autism spectrum with and without mitochondrial dysfunction.

Objectives: While the ultimate goal is to understand how OXPHOS defects relate to neurologic features of some children with ASD, there is an immediate need for qualitative descriptions regarding the similarities and differences between these two patient groups. Preliminary observations from our lab suggest that children with comorbid ASD and OXPHOS mitochondrial disease exhibit less consistent social deficits. Specifically, clinically important distinctions may be observed in diagnostic tools such as the Autism Diagnostic Interview, Revised (ADI-R; Rutter, LeCouteur, & Lord, 2003). 

Methods:   Children with a diagnosis of ASD alone (n = 19; 2 female; M_age = 9.60, SD_age = 1.79) and with a comorbid diagnosis of ASD and mitochondrial disease (n = 16; 2 female; M_age = 8.87, SD_age = 2.16) between the ages of 5 and 11 were recruited for participation in two independent fMRI studies investigating emotion processing and working memory, respectively. The comorbid diagnostic participants are part of a current ongoing research project, whereas the participants with known ASD only were included from a project ending in 2010. Each child’s primary caregiver completed the ADI-R with a reliably trained graduate student or licensed psychologist in person or over the phone. The ADI-R Diagnostic Algorithm and total domain scores were used for the current analyses.

Results: Independent samples t tests were used to compare total scores between ASD only vs. comorbid ASD and mitochondrial patients’ ADI-R total scores. The two groups did not differ with respect to age, t(33) = -1.10, p = .28. Patients with ASD alone were reported by their caregiver to demonstrate more severe social deficits (M_ASD = 19.63; M_MITO = 13.94), t(33) = 2.21, p = .034, η² = .13, as evidenced by ADI-R total Social Deficits domain score. Significant differences were not observed for the Communication Deficits domain score, t(33) = 1.53, p = .14, η² = .07, or the Restricted/Repetitive Behavior domain score, t(33) = 1.16, p = .25, η² = .04.  

Conclusions:   According to caregiver report on the ADI-R, it appears that children diagnosed with comorbid ASD and mitochondrial disease presented, on average, with less severe social deficits during their early social development. These data corroborate preliminary observations of work in our lab with children who have comorbid ASD and OXPHOS mitochondrial disease and suggest that further research is warranted investigating the interaction of OXPHOS or mitochondrial defects and ASD symptomatology.