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TMLHE deficiency and a carnitine hypothesis for autism

State/Province Full: 
United States

This Pilot study follows up on a publication entitled "A novel X-linked inborn error of carnitine biosynthesis and a neuronal carnitine pathway hypothesis for autism." This paper describes a new genetic condition (called TMLHE deficiency) that results in the loss of ability to make carnitine in the body. Carnitine is a nutrient that is taken in in the diet but also can be made in the body. The carnitine content of red meats is very high while that of vegetables is very low. The TMLHE gene is on the X-chromosome so that it is sex-linked and occurs predominantly in males. This inability to make carnitine is very common at about 1 in 400 normal males. There a frequent mutation (abnormality causing loss of activity) that is 3.7 times more frequent in brother-brother pairs with autism compared to control males (p = 0.012). TMLHE deficiency is present in 0.5-1% of autism cases. The fact that many healthy adult males also have TMLHE deficiency may be explained by differences in carnitine intake in infancy. The TMLHE has high activity in brain suggesting that carnitine or related chemicals may be important for brain function. It is proposed a neuronal carnitine pathway hypothesis that implies that a significant fraction of non-dysmorphic autism (NDA) is caused by abnormalities of carnitine metabolism with a major gene-diet interaction. They also propose that the hypothesis is testable by analysis of carnitine metabolites in cerebrospinal fluid (CSF) and by clinical trials of carnitine supplementation. Non-dysmorphic autism refers to autistic children who do not have birth defects and whose body and face look normal. This Pilot study aims to expand the information about the role of the TMLHE gene in autism. The research has the potential to show that the 0.5 to 1% of autism that is associated with TMLHE deficiency will be preventable and partially reversible at early ages through carnitine supplementation. This study has the potential to support research that tests the hypothesis that some larger fraction of NDA can be prevented or reversed through carnitine related therapy.