Research

An Educational Webinar about Autism and Mitochondrial Function

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Evaluation and Treatment of Patients with Autism and Mitochondrial Disease

Richard I. Kelley, MD, PhD
Division of Metabolism, Kennedy Krieger Institute
Department of Pediatrics, Johns Hopkins Medical Institutions

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I. Introduction and Background

Our clinical experience at Kennedy Krieger Institute over the last 15 years has shown that a deficiency of mitochondrial complex I is a common cause of regressive autism. Although some clinical characteristics of mitochondrial disease, such as mild gross motor delay and hypotonia, are sometimes manifest, the abnormalities typically are subtle and not appreciated until there is loss of language and regression of social development, most commonly at the time of an otherwise simple childhood infection. Most children with autism secondary to mitochondrial disease […]

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Autism and Mitochondrial Disease

(University of California, San Diego, CA)

Abstract
Autism spectrum disorder (ASD) as defined by the revised Diagnostic and Statistical Manual of Mental Disorders: DSM IVTR criteria (American Psychiatric Association [2000] Washington, DC: American Psychiatric Publishing) as impairment before the age of 3 in language development and socialization with the development of repetitive behaviors, appears to be increased in incidence and prevalence. Similarly, mitochondrial disorders are increasingly recognized. Although overlap between these disorders is to be expected, accumulating clinical, genetic, and biochemical evidence suggests that mitochondrial dysfunction in ASD is more commonly seen than expected. Some patients with ASD phenotypes clearly have genetic-based primary mitochondrial disease. This review will examine the data […]

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Relative Carnitine Deficiency in Autism

(University of California, Irvine, CA)

Abstract
A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine (p < 0.001), and pyruvate (p = 0.006) were significantly reduced while ammonia and alanine levels were considerably elevated (p < 0.001) in our autistic subjects. The relative carnitine deficiency in these patients, accompanied by slight elevations in lactate and significant elevations in alanine and ammonia levels, is suggestive of mild mitochondrial dysfunction. It is hypothesized that a mitochondrial defect may be the origin of […]

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Mitochondrial dysfunction in autism spectrum disorders: a population-based study

(Outpatient Clinic of Autism, Portugal)

Abstract
A minority of cases of autism has been associated with several different organic conditions, including bioenergetic metabolism deficiency. In a population-based study, we screened associated medical conditions in a group of 120 children with autism (current age range 11y 5mo to 14y 4mo, mean age 12y 11mo [SD 9.6mo], male:female ratio 2.9:1). Children were diagnosed using Diagnostic and Statistical Manual of Mental Disorders criteria, the Autism Diagnostic Interview–Revised, and the Childhood Autism Rating Scale; 76% were diagnosed with typical autism and 24% with atypical autism. Cognitive functional level was assessed with the Griffiths scale and the Wechsler Intelligence Scale for Children and was in the […]

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Mitochondrial dysfunction in autism spectrum disorders: Cause or effect?

(University of Bari, Italy)

Abstract
Autism Spectrum Disorders encompass severe developmental disorders characterized by variable degrees of impairment in language, communication and social skills, as well as by repetitive and stereotypic patterns of behaviour. Substantial percentages of autistic patients display peripheral markers of mitochondrial energy metabolism dysfunction, such as (a) elevated lactate, pyruvate, and alanine levels in blood, urine and/or cerebrospinal fluid, (b) serum carnitine deficiency, and/or (c) enhanced oxidative stress. These biochemical abnormalities are accompanied by highly heterogeneous clinical presentations, which generally (but by no means always) encompass neurological and systemic symptoms relatively unusual in idiopathic autistic disorder. In some patients, these abnormalities have been successfully explained by the presence […]

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Neurometabolic disorders and dysfunction in autism spectrum disorders

(National Institutes of Mental Health, Bethesda, MD)

Abstract
The cause of autism remains largely unknown because it is likely multifactorial, arising from the interaction of biologic, genetic, and environmental factors. The specific role of metabolic abnormalities also is largely unknown, but current research may provide insight into the pathophysiologic underpinnings of autism, at least in some patients. We review a number of known neurometabolic disorders identified as having an autistic phenotype. We also discuss the possible involvement of mitochondrial disorders and dysfunction as well as a theory regarding an increased vulnerability to oxidative stress, by which various environmental toxins produce metabolic alterations that impair normal cellular function. Finally, we review various […]

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Mitochondrial DNA abnormalities and autistic spectrum disorders

(Columbia University, New York)

Abstract

OBJECTIVES:
To further characterize mtDNA defects associated with autistic features, especially the A3243G mtDNA mutation and mtDNA depletion.Study design Five patients with autistic spectrum disorders and family histories of mitochondrial DNA diseases were studied. We performed mtDNA analysis in all patients and magnetic resonance spectroscopy in three.

RESULTS:
Three patients manifested isolated autistic spectrum features and two had additional neurologic symptoms. Two patients harbored the A3243G mutation. In two others, the A3243G mutation was not found in accessible tissues but was present in tissues from their mothers. The fifth patient had 72% mtDNA depletion in skeletal muscle.

CONCLUSIONS:
Autistic spectrum disorders with or without […]

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A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures.

(International Child Development Resource Center, Melbourne, FL)

Abstract
Recent studies have implicated physiological and metabolic abnormalities in autism spectrum disorders (ASD) and other psychiatric disorders, particularly immune dysregulation or inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures (‘four major areas’). The aim of this study was to determine trends in the literature on these topics with respect to ASD. A comprehensive literature search from 1971 to 2010 was performed in these four major areas in ASD with three objectives. First, publications were divided by several criteria, including whether or not they implicated an association between the physiological abnormality and ASD. A large percentage of publications implicated an association between ASD […]

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Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis.

(International Child Development Resource Center, Melbourne, FL)

Abstract
A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (≈ 0.01%). The prevalence of abnormal biomarker values of mitochondrial […]

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If you would like more information on the use of MitoSpectra in clinical practice or are interested in participating in the research or educational activities of MitoMedical, please email Dr. Suzanne Goh at sgoh@mitomedical.com