Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

Fragile X and glutamate

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This is another one for the ‘autism is all about glutamate’ file.

Fragile X syndrome is an X-linked syndrome with physical characteristics, mental retardation and autism.

Boys with the syndrome may have large testicles (macroorchidism), prognathism, hypotonia and autism, and a characteristic but variable face with large ears, long face, high-arched palate, gynecomastia, and malocclusion. Additional abnormalities may include lordosis, heart defect, pectus excavatum, flat feet, shortening of the tubular bones of the hands, and joint laxity. Females who have one fragile chromosome and one normal X chromosome may range from normal to mild manifestations of the fragile X syndrome.

The genetics of Fragile X are quite straightforward:

The fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X chromosome. Mutation at that site is found in 1 out of about every 2000 males and 1 out of about every 259 females. (Incidence of the disease itself is about 1 in every 4000 females.)

Normally, the (FMR1 gene contains between 6 and 55 repeats of the CGG codontrinucleotide repeats). In people with the fragile X syndrome, the FMR1 allele has over 230 repeats of this codon.

Expansion of the CGG repeating codon to such a degree results in a methylation of that portion of the DNA, effectively silencing the expression of the FMR1 protein.

This methylation of the FMR1 locus in chromosome band Xq27.3 is believed to result in constriction of the X chromosome which appears ‘fragile’ under the microscope at that point, a phenomenon that gave the syndrome its name.

Mutation of the FMR1 gene leads to the transcriptional silencing of the fragile X-mental retardation protein, FMRP. In normal individuals, FMRP binds and facilitates the translation of a number of essential neuronal RNAs. In fragile X patients, however, these RNAs are not translated into proteins. Fragile X Wiki

Today Grey Matter/White Matter linked to a press release reporting new progress in fragile X research.

ATLANTA, March 10 (UPI) — A U.S. team of scientists has identified several drugs and small molecules that reverse features of fragile X syndrome — a form of mental retardation.

The scientists, led by Stephen Warren of Emory University, made their discoveries using a new drug screening method in Drosophila (fruit flies), setting the stage for development of new treatments for the syndrome, one of the leading known causes of autism.

Warren led a group of scientists that discovered in 1991 that the FMR1 gene is responsible for fragile X syndrome.

In the current experiment, scientists discovered when FMR1-deficient fly embryos were fed food containing increased levels of glutamate, they died during development.

The scientists placed the FMR1-deficient fly embryos in thousands of tiny wells containing food with glutamate. In addition, each well contained one compound from a library of 2,000 drugs and small molecules. Using that screening method, the scientists uncovered nine molecules that reversed the lethal effects of glutamate.

The study that included Shuang Chang, Steven Bray and Peng Jin of Emory, Zigang Li of the University of Chicago and Daniela Zarnescu from the University of Arizona appears online in the journal Nature Chemical Biology. Progress reported in fragile X research

In a longer news article we find:

A variety of scientific evidence suggests that increasing glutamate neuronal transmission may be beneficial in autism and in fragile X syndrome. Imaging studies demonstrate that areas of the brain that are extremely rich in glutamate transmission are less active in autistic patients. Molecular studies suggest that although genes involved in the AMPA-type glutamate receptor are more active in autistic patients, the density of AMPA-type glutamate receptors is decreased. Drugs that reduce glutamatergic transmission induce symptoms similar to those seen in autistic patients. Taken together, these facts suggest that enhancing AMPA receptor activity may be beneficial in autistic patients. New Drug That Enhances Glutamate Transmission In The Brain Being Evaluated For Fragile X

Wikipedia also mentions:

One hypothesis is that many symptoms are caused by unchecked activation of mGluR5, a metabotropic glutamate receptor, which was found in a 2007 study to contribute significantly to the pathogenesis of the disease; this suggests that mGluR5 blockers could be used to treat fragile X syndrome.

I do not have fragile X syndrome. But dietary free glutamate makes me very withdrawn and inhibited and later incredibly sleepy, so there is clearly something going on with the way I process and use glutamate. Glutamate is also implicated in autism through the gene for neurexin 1.

Wake up folks! It’s still not mercury.

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Written by alienrobotgirl

11 March, 2008 at 11:41 am

Posted in Autism Genetics

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