Asparagine is considered to be a non essential amino acid. The protein is found in meat, dairy and nuts. Scientists have discovered that a recessive gene mutation that affects the synthesis of asparagine affects the crucial development of normal brain development and function.
Genetic researchers at Duke Medicine published their findings in the Neuron journal on the 16th of October. The investigation into the non essential amino acid began when two separate families in Israel, both of Iranian Jewish ancestry, had children with small head circumference that grows progressively worse, accompanied by profound developmental delays and seizures.
Goldstein and his colleagues analyzed gene variants that were shared by the two children affected by the abnormal brain development but did not occur in the normal population. The mutation directly linked to the childrens’ condition was located in the asparagine synthetase gene, or ASNS, which controls the production of the metabolite asparagine from other amino acids.
Two other families located in Canada had children who were born with similar problems. Genetic Analysis pointed to the mutations in the same ASNS genes.
By investigating the cases, researchers discovered that each of the parents in these four families shared a rare recessive trait that, by chance, combined to result in a newly identified developmental disorder in their children. More cases are likely to come to light now that the gene mutation has been identified.
“This non-essential amino acid has different levels inside and outside the central nervous system, and it may be that in the central nervous system, it plays a critical role,” said David B. Goldstein, Ph.D., director of the Center for Human Genome Variation and professor of Molecular Genetics & Microbiology and professor of biology at Duke University School of Medicine. “What is exciting about this is if we can work out how it functions, a treatment might be asparagine supplementation in the diet.”
Goldstein pointed out that other similar deficiencies in amino acids synthesization all causing neurological problems have recently been identified. These conditions have shown improvement with the use of dietary supplements, suggesting that the impairments caused by the ASNS mutation might benefit from asparagine supplementation.
“An emerging theme is that with these ‘non-essential’ amino acids, their metabolism does matter,” Goldstein said. “This metabolic pathway is important, and it may be that the amount of asparagine is the key, or a buildup of toxin in that pathway caused by the mutation.”
Elizabeth K. Ruzzo, José-Mario Capo-Chichi, Bruria Ben-Zeev, David Chitayat, Hanqian Mao, Andrea L. Pappas, Yuki Hitomi, Yi-Fan Lu, Xiaodi Yao, Fadi F. Hamdan, Kimberly Pelak, Haike Reznik-Wolf, Ifat Bar-Joseph, Danit Oz-Levi, Dorit Lev, Tally Lerman-Sagie, Esther Leshinsky-Silver, Yair Anikster, Edna Ben-Asher, Tsviya Olender, Laurence Colleaux, Jean-Claude Décarie, Susan Blaser, Brenda Banwell, Rasesh B. Joshi, Xiao-Ping He, Lysanne Patry, Rachel J. Silver, Sylvia Dobrzeniecka, Mohammad S. Islam, Abul Hasnat, Mark E. Samuels, Dipendra K. Aryal, Ramona M. Rodriguiz, Yong-hui Jiang, William C. Wetsel, James O. McNamara, Guy A. Rouleau, Debra L. Silver, Doron Lancet, Elon Pras, Grant A. Mitchell, Jacques L. Michaud, David B. Goldstein. Deficiency of Asparagine Synthetase Causes Congenital Microcephaly and a Progressive Form of Encephalopathy. Neuron, 2013; 80 (2): 429 DOI: 10.1016/j.neuron.2013.08.013