Conditions comorbid to autism spectrum disorders
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that begins in early childhood, persists throughout adulthood, and affects two crucial areas of development: social communication and restricted, repetitive patterns of behavior.[1] There are many conditions comorbid to autism spectrum disorder such as attention-deficit hyperactivity disorder and epilepsy.
In medicine and in psychiatry, comorbidity is the presence of one or more additional conditions co-occurring with the primary one, or the effect of such additional disorders. About 10–15% of autism cases have an identifiable Mendelian (single-gene) condition, chromosome abnormality, or other genetic syndrome,[2] a category referred to as syndromic autism. ASD is associated with several genetic disorders,[3] perhaps due to an overlap in genetic causes.[4]
Distinguishing between ASD and other diagnoses can be challenging because the traits of ASD often overlap with symptoms of other disorders and the characteristics of ASD make traditional diagnostic procedures difficult.[5][6]
Comorbid conditions[edit]
Abnormal folate metabolism[edit]
Several lines of evidence indicate abnormalities of folate metabolism in ASD. These abnormalities can lead to a decrease in 5-methyltetrahydrofolate production, alter the production of folate metabolites and reduce folate transport across the blood-brain barrier and in neurons. The most significant abnormalities of folate metabolism associated with ASD may be autoantibodies to the alpha folate receptor (FRα). These autoantibodies have been associated with cerebral folate deficiency. Autoantibodies can bind to FRα and greatly impair its function.
In 2013, one study reported that 60% and 44% of 93 children with ASD were positive for FRα-blocking and binding autoantibodies, respectively. This high rate of anti-FRα autoantibody positivity was confirmed by Ramaekers et al. who compared 75 children with ASD to 30 non-autistic "controls". These controls were children who had a developmental delay, but did not have ASD. FRα-blocking autoantibodies were positive in 47% of children with ASD, but only in 3% of children without ASD.
Many children with ASD and cerebral folate deficiency have marked improvements in their clinical status when taking folinic acid.
A series of five children with cerebral folate deficiency and low functioning autism with neurological deficits found a complete reduction of ASD symptoms with the use of folinic acid in a child and substantial improvements in communication in two other children.[7]
Abnormal redox metabolism[edit]
An imbalance in glutathione-dependent redox metabolism has been shown to be associated with autism spectrum disorder (ASD). Glutathione synthesis and intracellular redox balance are related to folate metabolism and methylation, metabolic pathways that have also been shown to be abnormal in ASD. Together, these metabolic abnormalities define a distinct endophenotype of TSA closely associated with genetic, epigenetic and mitochondrial abnormalities, as well as environmental factors related to ASD. Glutathione is involved in neuroprotection against oxidative stress and neuroinflammation by improving the antioxidant stress system.
In autistic children, studies have shown that glutathione metabolism can be improved: