Getting more of the amino acid carnitine before and during pregnancy, likely from a supplement, could be a way to protect children from a certain type of autism. High levels of carnitine can be found in red meat, and one of the best vegetarian sources is whole milk. It’s also currently available as a supplement.
Carnitine, which the body can manufacture itself or extract from dietary sources, is required for transport of fatty acids into mitochondria—the compartment within the cell that converts these fats into energy.
Previous studies have shown that inherited mutations in a gene (called TMLHE) that is required for carnitine biosynthesis are strongly associated with risk for development of autism spectrum disorders, but the basis for that association has been unclear—until now.
The latest findings show that genetic defects in the body’s ability to manufacture carnitine might be associated with an increased risk of autism because carnitine deficiency interferes with the normal processes by which neural stem cells promote and organize embryonic and fetal brain development.
Neural Stem Cells
Zhigang Xie, an assistant research scientist at the Texas A&M Health Science Center College of Medicine, has refined a new technology that allows him to mark, follow, and analyze individual neural stem cells in their native environment in a real developing brain.
“It’s very difficult to study neural stem cells in their complex natural environment,” says Xie. “But now we have a technology that makes such studies possible.”
Xie and colleagues found that neural stem cells unable to produce carnitine don’t behave properly and are inappropriately depleted from the developing brain, but when genetically at-risk neural stem cells are supplied with carnitine from an outside source, they don’t have the same problems.
Without getting too technical, the autism-associated TMLHE gene encodes an enzyme that the body needs to manufacture carnitine. Autism risk mutations inactivate this gene and, in the absence of their own ability to produce carnitine and without adequate outside supplementation, neural stem cells become less efficient at self-renewal.
That is, when they divide, neural stem cells produce two “daughter” cells, one of which should remain a neural stem cell and the other that should differentiate. Neural stem cells confronted with carnitine deficiency too often divide to produce two differentiated cells, thereby failing to resupply the developing brain with a cache of neural stem cells.
“Inborn errors in carnitine production cause significant issues in a cell type one would believe has to contribute to autism risk,”
says Vytas A. Bankaitis, a chemistry professor and collaborator on the study.
Genetic Test for Prospective Mothers
As the autism risk gene is located on the X chromosome and males have only one X chromosome (females have two), they are at greater risk.
Some pregnant women might absorb enough carnitine from their diet so as to make normal enzyme function less important in the context of autism risk for their babies.
Because the TMLHE is a recognized autism risk gene and its location on the chromosome is known, one possible first step for prevention is to test prospective mothers for TMLHE mutations before pregnancy.
If a prospective mother is a carrier for the mutated autism risk gene, supplementation of her diet with carnitine before and during pregnancy could help ensure that a sufficient supply of the nutrient is available to the developing embryo and fetus, thus helping to offset the genetic defect.
“In retrospect, this preventative approach seems obvious,” Bankaitis says. “But, metabolic deficiencies are complicated scenarios to interpret, and we believe these complexities obscured what will hopefully prove to be a rather simple path towards prevention.”
It’s important to note that this particular prevention strategy will not apply to all cases of autism.
“Even if this strategy works, it will not be a panacea for reducing all autism risk,” Bankaitis says. “While it could work in cases involving carnitine-deficiency, other pathways are also in play because as many as 1000 genes might ultimately be found to relate to autism risk.
Still, the potential impact of even such a limited preventive strategy could be significant as mutant TMLHE alleles are surprisingly common in the human population.”
“Here we have indications, at least for some types of autism risk, that a dietary carnitine prevention method might be effective,” Xie says. “For some individuals, this simple nutritional supplement might really help reduce the risk of developing autism spectrum disorder. Any progress on the prevention front would be welcome given the number of people affected.”
Xie, Zhigang et al.
Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism
Cell Reports DOI: http://dx.doi.org/10.1016/j.celrep.2016.01.004
Image: Chris Nurse, Wellcome Images