NKH is a rare genetic disorder that affects 1 child in every 60,000 born. Children with this condition have a problem breaking down the amino acid glycine. This is caused by a defect in the genetic code for the machinery that is responsible for the glycine breakdown (called glycine cleavage enzyme). Amino acids are natural components of our body. Because glycine is not broken down, it accumulates in the body. Glycine is an important molecule in the brain where it has various functions such as transmitting signals from one brain cell to another. Excessive glycine disrupts the function of the brain.
Children with NKH usually present as newborns, but 1 in 5 children presents in infancy. Typical symptoms include seizures, low tone, and severe problems with learning and development. This can profoundly affect a child’s ability to learn and to do normal things such as eating, sitting, and walking. The seizures can be so severe that they are hardly controlled despite the use of several medications for seizures. Not all children are equally affected. Most commonly children are severely affected and do not make developmental progress and have difficult to control seizures. Some children, about 1 in 6, are more mildly affected. They make progress in their development, and have seizures that can be controlled more easily. Current treatment is limited.
We assume, but have not completely proven, that the difference between severely affected children and more mildly affected children relates to the genetic defect. There is also some early evidence that the condition involves a loss of function that occurs in the first year of life. If so, then this indicate that the problems are not due to defects present before birth, but reinforce our hope that understanding this process will provide an opportunity to prevent the harm to the brain of these children from occurring. This process seems to happen in the more severely affected children.
In our current studies, we first aim to analyze what predicts if children are severely or more mildly affected with the condition. We try to provide the link between the genetic defect and the severity and to develop a practical method to study this difference. Second, we aim to look for clues to the mechanism that causes this disease. Only when we understand how the defect in the metabolism of glycine leads to the observed problems, can we develop rational interventions that will change the course of the disease. Such studies will involve analyzing samples from affected children. We also aim to study and animal that has this disease and that will allow us to directly investigate how this diseases affects the brain. Finally, we aim to review what the impact has been of the current existing treatment on the patients. We hope that this will provide the way with which we can develop a treatment that changes the course of the disorder for these unfortunate children.