Onset Patterns in ASD: Early Development, Later Outcomes and the Association with Mitochondrial Dysfunctions.

Background: Behavioral signs of ASD emerge through different patterns: early onset, regression and plateau. Regression is assumed to be characterized by a ‘typical’ development, followed by a loss of previously acquired skills at a mean age of 21 months in 33% of the children with ASD. Recently, a meta-analysis on mitochondrial dysfunctions (MD) in ASD demonstrated an overall prevalence of 5%. Children with ASD+MD showed more seizures, motor delay, gastro-intestinal abnormalities and an elevated lactate (a biochemical marker of MD). Furthermore, in 52% of the cases, regression was noted.
More insight into the course, prevalence and pathogenesis of onset patterns in ASD would be of significant diagnostic and clinical value.

Objectives: The first purpose is to explore the trajectories of onset patterns in ASD and long-term outcomes. Second, we want to examine the presence of MD and their association with the severity of ASD-symptoms and regression.

Methods: Participants were 100 children with ASD (M age=7.48y,sd=1.98,range=3-11y;70% boys). Parent report was used to measure early ASD-symptoms and classification to onset group (EDQ,ADI-R,RSQ). Non-verbal intelligence was measured through the WNV and current severity of ASD-symptoms by the ADOS-2. Screening of MD included measurement of lactate in urine and near-infrared spectroscopy (fNIRS) in the brain.

Results: The results revealed an early onset (≤12m;38%), a later onset (>12m;34%) and an early onset+regression group (10%). Other children had a typical development followed by regression (13%) or plateau (5%). Regression (M onset=22m) involved in 78% of the children loss of language skills. Children with regression (ASD-R) showed significantly lower non-verbal intelligence scores (M IQ=81.50,sd=21.47) compared to children without regression (ASD-NR;MIQ=93.04,sd=20.18;t(94)=2.321,p<.05). Examination of current severity of ASD-symptoms showed significantly more symptoms in ASD-R (U(98)=1152.5,p<.05).
Based on the lactate results, the children were divided into three groups: low lactate (n= 20;M=2.05mg/dL,sd=.84), medium lactate (n=58;M=5.45mg/dL,sd=1.75) and high lactate (n=20;M=11.52mg/dL,sd=2.55). Examination of early and current severity of ASD-symptoms showed no significant differences between the two extreme groups. Furthermore, no significant differences in non-verbal intelligence were found between the low (M IQ=87.37,sd=24.60) and the high lactate group (M IQ=90.75,sd=23.40; t(37)=.441;p=.662). The proportion of ASD-R did not differ between the high and the low lactate group (χ²(1)=3.135;p=.08). In addition, there was no significant difference between the lactate value of ASD-R (M=5.27mg/dL,sd=2.93) compared to ASD-NR (M=6.23mg/dL,sd=3.77;U(98)=757.5,p=.281). However, preliminary fNIRS results showed a significant difference between ASD-R and ASD-NR in the curves of the oxy-hemoglobin response in the temporal lobe of the right hemisphere (z=3.215;p<.05).

Conclusions: We found support for different onset patterns previously suggested in the literature. Further, ASD-R display more severe impairments later in life as measured by non-verbal IQ and ASD-symptomatology.
Based on lactate in urine as a biochemical marker of MD, no significant differences in the severity of ASD-symptoms and onset patterns were found. Still, there is a need for further examination since normal lactate levels have been reported in case studies of ASD+MD. Furthermore, preliminary analysis of fNIRS data showed a higher oxy-hemoglobin level in the brain of ASD-R. Final fNIRS results will be presented at the conference.