What is Nonketotic Hyperglycinemia?
Nonketotic Hyperglycinemia is a genetic metabolic disorder which prevents the body from processing glycine. Nonketotic Hyperglycinemia (NKH) is also known as Glycine encephalopathy.
What is Glycine, and what is it used for?
Glycine is an amino acid, the smallest amino acid there is. Known as the building blocks of life, amino acids are what makeup proteins and are crucial for almost every cell function in the body.
Glycine acts as a neurotransmitter, chemical signals found in the brain and central nervous system that runs throughout the body. It can also reduce activity in the spinal cord and brain stem while increasing activity in the brain cortex. This affects cognitive function, learning and retaining information. As a neurotransmitter, it is also vital in ensuring messages are transmitted correctly from the brain to other parts of the body.
Glycine is processed through the Glycine Cleavage System (GCS), which takes Glycine and creates ammonia and carbon dioxide.
What causes Nonketotic Hyperglycinemia?
NKH is a genetic disorder. There are several genes which tell the body how to process glycine, via the Glycine Cleavage System. With NKH, there is a mutation of genes which prevent the GCS from operating correctly, leading to the increase of glycine levels in the body.
To inherit the mutation, both parents carry one copy of the mutated gene. The child has inherited two copies of the mutated gene – one from each parent.
The Glycine Cleavage System
The glycine cleavage system (GCS, also known as the glycine decarboxylase complex or GDC) is a series of enzymes that are triggered when there are high levels of glycine. The GCS is loosely attached to the inner membrane of the mitochondria – the energy factory of a cell. You can read more about the Glycine Cleavage System here.
When there are elevated levels of glycine, it alters development, movement and intelligence. If it is not broken down, toxic levels build up blood, brain, spinal fluid, organs and tissues. This causes brain damage, difficult to control seizures, muscle weakness and/or spasticity. These lead to other medical issues – as an example: muscle weakness in the chest/lungs may make it difficult to breathe.
Types of NKH
The different categories of NKH – Classic vs Variant, Severe/Attenuated and Infantile vs Late Onset