Twin cities facing genetic disaster: Fumarase deficiency

Twin cities facing genetic disaster: Fumarase deficiency

Last Updated on August 5, 2017 by Joseph Gut – thasso

August 03, 2017 – Fumarase deficiency is extremely rare – until around 1990 there had only been 13 diagnosed and identified cases worldwide. Fumarase deficiency is an autosomal recessive metabolic disorder characterized by a deficiency of the enzyme fumarate hydratase, which is indicated by a buildup of fumaric acid in the urine. With only 13 reported cases of fumarase deficiency in the world, an individual would have a one-in-400 million chance of being affected by the condition.Not so in the border region of Arizona and Utah.  In recent years, a cluster of around 20 cases has been documented in the twin towns of Colorado City, Arizona and Hildale, Utah in the US among a community of the Fundamentalist Church of Jesus Christ of Latter Day Saints. On might say that the two cities are facing a genetic disaster of sorts.
Appearance of a fumarase deficient child.

The problem was first discovered in 1990, by Dr, Theodore Tarby who specialised in rare childhood diseases. This was after a woman in the community brought her 10-year-old son to him. Dr. Tarby recognised the boy’s unusual facial features, such as his low-set ears, widely-spaced eyes, small jaw and a prominent forehead. In addition to this, the boy was severely physically and mentally disabled.

An urine sample was taken and came back showing that the boy had a fumarase deficiency. Children suffering from the condition are often missing parts of their brain and can’t either sit or stand without support.Their IQ is usually around 25, and their language skills are minimal.

At the time, Dr. Tarby believed had all the reasons to believe that there were only 13 cases of fumarase deficiency in the world, and that he happened to just encounter one of those unbelievable rare cases.  As it turned out, this was not actually the case in that the 10-year-old’s sister, whom the parents believed was suffering from cerebral palsy also had the rare condition. Together with colleagues, Dr Tarby had soon diagnosed eight new cases within the same community, in children ranging from toddlers to 12-year-olds. Most of the patients couldn’t walk or sit up, while they all shared the same facial characteristics.

The likelihood of having the disease within this small community was over one million times the global average, researchers found. And the reason for this was the gradual inbreeding that had been and still is happening over generations in populations that exercise polygamy. With polygamy, the overall genetic diversity tends to notably  decrease because a few men are having a disproportionate impact on the next generation. Random genetic mutations become more important and their frequency may notably increase within such populations as compared to the general population. It’s now estimated that thousands of people in the 7,700-person community are carriers of the recessive yet defect gene.

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Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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