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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

TMLHE deficiency and a carnitine hypothesis for autism

Principal Investigator

Principal Investigator

Beaudet, Arthur

Description

Description

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.

Funder

Funder

Autism Speaks

Fiscal Year Funding

Fiscal Year Funding

0

Current Award Period

Current Award Period

2012-2014

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 2SD. Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g. Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. IACC Recommended Budget: $9,000,000 over 5 years.

Project Link

Project Link

TMLHE deficiency and a carnitine hypothesis for autism (External web link)

Institution

Institution

Baylor College of Medicine

State/Country

State/Country

Texas

Project Number

Project Number

7697

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

TMLHE deficiency and a carnitine hypothesis for autism | 60000 | 2012 | 7697
TMLHE deficiency and a carnitine hypothesis for autism | 60000 | 2013 | 7697

 
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