Autism spectrum disorders associated to a deficiency of the enzymes of the mitochondrial respiratory chain

Abstract

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by a combination of reciprocal social deficits, communication impairment, and rigid ritualistic interest and stereotypies. The etiology is generally multifactorial, including genetic, immunological and/or environmental factors. A group of ASD has been linked to mitochondrial dysfunction with subsequent deficiency in energy production. Patients with ASD and mitochondrial disease often show signs and symptoms uncommon to idiopathic ASD such as cardiac, pancreatic or liver dysfunction, cardiac, growth retardation, fatigability, but in some cases semiology is different. We show two clinical cases of ASD associated to a deficiency of the mitochondrial respiratory chain (complex I+III and IV) with different clinical presentations. In one case, signs and symptoms of mitochondrial disorder were mild and the second diagnosis was attained many years after that of ASD. These findings support the recent growing body of evidence that ASD can be associated with mitochondrial disorder. Children with ASD and abnormal neurologic or systemic findings should be evaluated for mitochondrial disorder.

Altered expression of Alzheimer’s disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy

“…34 Focused microarray analysis used in this study demonstrated that expression of 40% of the AD-related genes was altered in the cerebellum of autistic patients (corrected P -value <0.05), these changes mainly represented by downregulation of NADH dehydrogenases and cytochrome c oxidases (Table 1). These results reflect deficient mitochondrial respiratory chain that is consistent with recent reports describing mitochondrial dysfunction in ASD; 35 or may indirectly confirm tight Notch–mitochondria interconnections. 36 An upregulation of GRIN1 (corrected P -value=0.03916101), the channel-forming subunit NR1 of NMDA glutamate receptors and MAP3K1 (corrected P -value=0.038406592), also known as MEKK1 or MAPK/ERK Kinase Kinase 1 , which activates JNK and ERK pathways with anti-apoptotic effect, 37 were also found among the AD-related genes in ASD samples (Table 1).…”

Mitochondrial Enzyme Dysfunction in Autism Spectrum Disorders; A Novel Biomarker Revealed From Buccal Swab Analysis

“…These findings are consistent with a small-scale study using cultured lymphocytes, another peripheral tissue, in which significant RC abnormalities were reported in six out of ten ASD subjects [8]. Furthermore, the prevalence of mitochondrial dysfunction in ASD documented here may actually represent an underestimate since our analysis did not include the evaluation of less prevalent but potentially significant deficiencies in RC-II, RC-III and RC-V activities which have been also described in some ASD cases [1][2][3]8,21,22].…”

Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

“…Normally, low levels of this protein have been used as a biomarker for oxidative stress, diabetes and a risk factor for metabolic syndrome [35,36]. Therefore, this finding may be in contrast with the reported higher incidence of these conditions in ASD individuals [37,38]. However, this could also be due to the fact that most previous studies have not accounted for any differences in age-related trajectories.…”