Focusing on the SLC6A6 gene, which encodes a transporter protein that carries taurine which is an amino acid that is essential for functioning of the retina and cardiac muscle, where there are pathogenic mutations of this gene it was discovered that an individual will suffer from a lack of taurine and will gradually lose sight until becoming blind within a few years as well as developing a weak heart. It was hypothesized that a taurine supplement may compensate for this deficiency; to test this a supplement was given to a young girl suffering from the disease to help stop progression of visual degeneration and treat her cardiomyopathy; results are published in the journal Human Molecular Genetics.
Working in collaboration with scientists from Pakistan the genomes of 500 families with ill and healthy children were studied to identify as many genes as possible that can cause recessive genetic diseases. “We looked at Pakistani families because consanguineous marriage is still a common practice, with 50 percent of marriages taking place between first cousins,” explains Stylianos Antonarakis, emeritus professor in UNIGE’s Faculty of Medicine. “In fact, consanguinity increases the risk of developing a recessive genetic disease since about 12 percent of the genome is identical in cousins.”
One family of particular interest consisted of two parents being healthy first cousins with 4 children, two of which were ill, a 15 year old male who lost all vision with a few years and a 4 years old female who was gradually losing her vision but still able to make out colours and shapes. “With the help of the Khyber Medical University in Pakistan, we collected blood samples of each family member. Their genome sequencing showed that their illness was linked to a mutation of the SLC6A6 gene,” notes Muhammad Ansar, a researcher in the Genetics Department in UNIGE’s Faculty of Medicine.
SLC6A6 produces a protein of the cell membrane that transports taurine. “It’s a dietary supplement found in large quantities in certain energy drinks,” says Ansar. Those suffering with the disease have extremely low levels of taurine in their blood, and data showed the genetic abnormality in this family reduced the carrying capacity of taurine to that of 15% of its normal level in these children.
The researchers believed that it may be possible to block progression of the disease by administering a taurine supplement to the affected children, and the family was taken to Geneva to carry out detailed investigations into the rare genetic disease, where the visual progressive impairment was diagnosed to be total in the male child, while the female child still retained some vision, and damage to the cardiac muscle was diagnosed in both children.
“We gave 100 mg per kg of taurine daily to the children to be continued over the long-term, and organized regular ophthalmologic and cardiac monitoring sessions in Pakistan,” emphasizes Emmanuelle Ranza, a doctor and geneticist at University Hospitals Geneva (HUG) and UNIGE who was responsible for the clinical part of the study. After only 3 days taurine levels in the children’s blood increased from 6 to 85 μ mol/l to reach normal levels, and after 2 years the cardiomyopathy had completely disappeared from both children as well. Degeneration of vision in the female child was stopped and even improved to the point where she could move around by herself, but this was not possible for the male child who had already lost his entire retina.
“These results are exceptional, because it’s the first time a food supplement given orally has been used to treat the retina and the heart successfully,” points out Antonarakis. “This little girl has paved the way for a potential cure for newborns suffering from the same recessive disease. One patient can change the history of medicine!”
It is estimated that there may be 6,000 infants who may suffer from this same SLC6A6 related disease worldwide, with around 300 being in Europe and North America. “Our goal now is to detect newborns affected by the condition at an early stage so they can be treated from birth with a taurine supplement and potentially prevent the onset of symptoms,” adds Antonarakis.
The researchers plan to continue to try and identify other new genes that cause recessive diseases, being highly motivated by their proof of being able to effectively treat at least some of them.
