Saify, Mariya

Abstract Aims To compare the prevalence of autism spectrum disorder (ASD) in children with and without epilepsy using clinical diagnoses and chart review with research‐defined criteria and to examine sex ratios, age at ASD onset, and intellectual disability between groups. Method The Olmsted County birth cohort included 30 490 individuals, of whom 257 (0.84%) had epilepsy diagnosed before 19 years of age. The cohort was previously screened for ASD using three case definitions: research‐inclusive (ASD‐R I ), research‐narrow (ASD‐R N ), and clinically diagnosed ASD (ASD‐C). For those with ASD‐R I , we assessed sex, intellectual disability (IQ < 70), and age at ASD onset. Means and proportions are reported when available. Results ASD prevalence was significantly higher in participants with epilepsy across all definitions: ASD‐R I 21.4% versus 3.2%; ASD‐R N 14.0% versus 1.6%; and ASD‐C 7.9% versus 0.7%. Children with both epilepsy and ASD‐R I were more often female (38.2% vs 25.8%), had higher rates of intellectual disability (56.5% vs 15.4%), and met the ASD‐R I criteria at a younger age (mean 7 years 5 months vs 8 years 8 months). Interpretation Co‐occurring ASD and epilepsy are frequently associated with intellectual disability, earlier age at ASD diagnosis, and reduced male predominance.

Content available: Video

AbstractMetabolic pathways are known to generate byproducts—some of which have no clear metabolic function and some of which are toxic. Nicotinamide adenine dinucleotide phosphate hydrate (NAD(P)HX) is a toxic metabolite that is produced by stressors such as a fever, infection, or physical stress. Nicotinamide adenine dinucleotide phosphate hydrate dehydratase (NAXD) and nicotinamide adenine dinucleotide phosphate hydrate epimerase (NAXE) are part of the nicotinamide repair system that function to break down this toxic metabolite. Deficiency of NAXD and NAXE interrupts the critical intracellular repair of NAD(P)HX and allows for its accumulation. Clinically, deficiency of NAXE manifests as progressive, early onset encephalopathy with brain edema and/or leukoencephalopathy (PEBEL) 1, while deficiency of NAXD manifests as PEBEL2. In this report, we describe a case of probable PEBEL2 in a patient with a variant of unknown significance (c.362C>T, p.121L) in the NAXD gene who presented after routine immunizations with significant skin findings and in the absence of fevers.