You are what you eat: dietary intervention may reverse symptoms of a genetic mutation

meat platter

Down to the smallest molecule, everything in our human machinery has its rightful place, with rapid damage control should things get slightly out of hand; like gears in clockwork, we expect every gene to work perfectly. Sadly, nature’s engineering makes mistakes sometimes, causing disorders such as the rare, but nonetheless debilitating Kabuki syndrome. This disorder presents itself as intellectual disability, growth retardation, immunological dysfunction and characteristic facial features. In an attempt to rectify this error in nature’s assembly of the genome that leads to Kabuki syndrome, a recent study lead by Dr Benjamin discovered that instead of using costly drug interventions, the disorder may be manageable through dietary intervention.

Kabuki syndrome stems from a mutation in one of two genes known as KMT2D and KDM6A, which both create enzymes that are involved in allowing other genes to be read and converted to proteins. When these enzymes are lacking, the chromatin, which compresses strands of DNA like a .zip file, cannot be unzipped, thus preventing that particular file of DNA from being read and used to make important proteins. A previous study had looked at using drugs that allow the chromatin to be opened, thereby circumventing the need for these enzymes.

Recently, a natural metabolic by-product of the liver has been identified, beta-hydroxybutyrate (BHB), which belongs to a group of molecules known as ketone bodies. BHB may have similar effects to the previously tested drugs that open chromatin. Additionally, BHB can enter the nervous system and therefore act on target areas of the brain, such as the hippocampus, the memory card of the brain.

Therefore, Dr Benjamin and his team investigated whether the memory defects of Kabuki syndrome can be alleviated, not with drugs, but with diet. Indeed, after two weeks of a ketogenic diet (a food regimen containing high levels of fatty acids which are metabolised to ketone bodies by the liver), the abnormal chromatin behaviour was alleviated in the hippocampi of mice with Kabuki syndrome. A similar effect was also seen when BHB was administered directly, demonstrating that the increase in BHB via diet may rescue the memory aspect of the disorder.

This study is the first evidence that a genetic disorder such as Kabuki syndrome can be managed through dietary manipulation, and may pave the way for other approaches to similar disorders.


About Danny Schnitzler

Danny Schnitzler is working as research assistant at the University of Edinburgh, Scotland on the role of oxytocin in feeding behaviour, while applying for PhD funding. Her scientific passion is neuroendocrinology, which looks at the role of hormones in the brain. In particular, she has an interest in how sex hormones act on neurophysiolgy. Outside of the lab, Danny is involved in addressing the gender imbalance in many aspects of STEM, public engagement and science communication. She also does "normal" fun things like going for runs, reading books and petting dogs.

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