Affiliations: Arkansas Children's Hospital Research Institute,
Department of Pediatrics, University of Arkansas for Medical Sciences, Little
Rock, AR, USA | Rossignol Medical Center, Irvine, CA, USA
Note: [] Corresponding author: Richard E. Frye, MD, PhD, Arkansas
Children's Hospital Research Institute, Little Rock, AR 72202, USA. Tel.: +1
501 364 4662; Fax: +1 501 978 6483; E-mail: [email protected]
Abstract: Recent research has implicated systematic physiological and
metabolic abnormalities, such as immune dysregulation, inflammation, oxidative
stress, mitochondrial dysfunction and other metabolic disorders that transcend
organ specific dysfunction in ASD. In this context, ASD may arise from, or at
least involve, systemic physiological abnormalities. In this review, common,
and not so common, metabolic abnormalities associated with ASD are outlined.
Mitochondrial dysfunction and cerebral folate abnormalities are the most
prevalent metabolic disorders affecting children with ASD. Other potentially
important metabolic disorders that have been reported in ASD include urea cycle
disorders, succinic semialdehyde dehydrogenase deficiency, adenylosuccinate
lyase deficiency, phenylketonuria, creatine deficiency syndromes, pyridoxine
dependent and responsive seizures, biotinidase deficiency and Smith-Lemli-Opitz
syndrome. Other metabolic abnormalities that appear to be associated with ASD
are disorders of general cholesterol metabolism and tetrahydrobiopterin
metabolism. Although detailed cases of children with ASD and these latter two
metabolic abnormalities have not been formally described, there is evidence
that some children with ASD may manifest these metabolic abnormalities. Lastly,
an algorithm for systematically approaching the diagnosis of metabolic disease in ASD is provided.
