NOTE: We excerpted this article by Lisa Ackerman of TACA. Please visit and bookmark TACA as a top resource for your loved one with autism's well being, growth, safety and success.
A recent study demonstrated that a blood test might be able to differentiate children with autism spectrum disorder (ASD) from typically developing children.1 The study examined one carbon metabolism and its related pathways. These pathways are of the upmost importance in ASD and are essential for many critical processes in the cells of the body, including methylation which regulates turning genes on and off, producing the precursors to genetic material and producing the major antioxidant in the body known as glutathione.2
This news is not really new, however the dataset’s potential predictive ability is intriguing. Over a decade ago, Dr. Jill James, demonstrated that children with ASD have abnormal one carbon metabolism and suggested that these metabolic markers define an endophenotype (subgroup) of children with ASD.3 Furthermore, Dr. James demonstrated that several common variations in genes which provide the instructions for cellular proteins and enzymes result in an increase in the risk of developing ASD with these variations interacting in complex ways.3 This suggests several “kinks” in these metabolic pathways may add up to predispose a child to develop ASD.
The metabolic markers found in this recent study are linked to oxidative stress – a finding that has been verified again and again. Oxidative stress is a process in which toxic molecules damage parts of the cell. Studies have demonstrated that key parts of the cell, which include: proteins such as those important for making the machinery of the cells’ enzymes, fats that are essential for making the membranes that define the cellular structure, and genetic material that encodes the cellular instructions, are all damaged by oxidative stress in children with ASD.2 Markers of oxidative damage have been found in many parts of the body in children with ASD, including immune cells4 and brain tissue.5 In addition, this oxidative stress has been associated with inflammation in children with ASD.6 In addition, we have recently demonstrated that oxidative stress can negatively affect mitochondrial function in children with ASD.7-9 Therefore, oxidative stress represents a potential cause of both the abnormal biochemistry and behavioral features reported in some individuals with autism.
One of the wonderful possibilities of identifying metabolic abnormalities is that they are potentially treatable. Based on observations from clinicians, Dr. Jill James demonstrated that a simple and safe treatment of three times a week injected Methyl-B12 and daily oral folinic acid could improve these abnormalities in metabolism.10 Later our research group at Arkansas Children’s Research Institute (ACRI) further demonstrated that this improvement was related to substantial improvements in development and behaviors.11 Dr. Robert Hendren at the University of California – San Francisco (UCSF) has further verified this finding in a double-blind placebo-controlled study using Methyl-B12 in individuals with autism.12
Our research team at ACRI recently demonstrated the importance of folate, the key nutrient of one-carbon metabolism, in the treatment of ASD in several studies. Several years ago Dr. Dan Rossignol and myself demonstrated that many children with ASD, possibly up to 75%, have a block in their ability to transport folate into the brain because of an autoantibody to the folate receptor alpha.13 Other studies have suggested that children with this blockage may have particular clinical characteristics14 and that these autoantibodies may affect the development of the thyroid.15 Recently our research team demonstrated that children with this block in folate transport may respond to a special type of reduced folate known as folinic acid (also known as leucovorin calcium) without measurable adverse effects.16 Our group at ACRI also recently showed that folate supplementation positively influences mitochondrial function.17
Interestingly, some of the same abnormalities and treatments that are related to ASD are also found during the prenatal period. For example, Dr. James demonstrated that one of the same variations in genes found in children with ASD also predispose children to develop ASD if they are found in the child’s mother.18 It is also intriguing and of note that the folate receptor alpha autoantibody is linked to birth defects when found in the mother and a recently developed animal model demonstrates that these autoantibodies in mother rodents result in ASD like behaviors in the offspring,19 with folate supplementation and an immune modulating therapy reversing this effect.20 Additionally, several studies have demonstrated that folate supplementation during pregnancy decreases the risk of developing autism.21,22
Read more at the TACANOW blog here.