Tourette's Syndrome Linked to Faulty Histamine Production

Tourette's Syndrome Linked to Faulty Histamine Production

A new study published in The New England Journal of Medicine suggests that Tourette's syndrome may be linked to defunct histamine signaling.

Tourette's syndrome is disorder marked by involuntary movements, or tics, that last more than a year. Tics can affect the motor movement of almost any area of the body. Tics can also be verbal, and can involve shouting or grunting involuntarily. Tourette's can be treated with both psychological and pharmacological therapy. Interestingly, the syndrome is thought to afflict men at a higher rate than women, although it does not discriminate against ethnic origin.. Although genetics are thought to play a strong role in the development of Tourette's, little is known about specific genes or the molecular origin of the disease. A new study published in The New England Journal of Medicine suggests that histamine signaling may play a significant role in the disorder.

The investigators analyzed DNA sequences from an afflicted father and 8 of his afflicted offspring, in addition to the unaffected mother. The authors found an area on chromosome 15 likely to carry a mutation in the children and father, but not in the mother. Ultimately, this mutation was found in the L-histadine decarboxylase gene, which is responsible for the synthesis of histamine. The mutation produces a premature stop codon in the enzyme, leading to the production of a truncated protein.

The investigators next performed a series of experiments to assess what role the mutation in L-histadine decarboxylase played in regards to its function. The authors used histadine labeled with a fluorescent marker. When converted to histamine, florescence would be undetectable. In the presence of the wild type enzyme, histadine was converted to histamine over time and fluorescence was lost. However, with the mutant enzyme, no fluorescence was lost. This suggests that the mutation in the enzyme leads to a non-functional truncated gene.

The authors point out that L-histadine decarboxylase is expressed in a specific portion of the brain and is responsible for producing histamine as a neurotransmitter. The receptors for histamine in the brain are known to regulate the sleep wake cycle and behavior; suggesting this pathway is a potential therapeutic target for the treatment for Tourette's. Although promising, this work confirms that further work in studying histamine signaling and its relation to Tourette's is needed.

References:

L-histidine decarboxylase and Tourette's syndrome. Ercan-Sencicek AG et, al. N Engl J Med. 2010 May 20;362(20):1901-8.