Diagnosis Methods

If your medical team suspect that there is a chance you or your child has NKH, they will confirm this using one or two of the following
measures:

• Levels of glycine in the blood, urine and cerebrospinal fluid (the fluid that surrounds the brain). If there is much more glycine in the cerebrospinal fluid and blood than normal amounts, this is a strong sign that the patient has NKH.
  
• Genetic testing will look for mutations in the DNA that affect the Glycine Cleavage System (GCS). NKH patients will often have two mutations in the genes that support the GCS – typically in the GLDC or AMT genes.
  
• Live Biopsy. Very rarely, a test called an enzyme assay might be done on a liver biopsy (this is where a small section of the liver is removed). An enzyme assay is a way to measure the chemical reactions in our bodies. This is not done very often, as genetic testing is considered less painful with less side effects.

Sometimes brain MRI scanning can be useful in identifying changes that are commonly seen in NKH patients (such as a thin corpus
callosum – also known as agenesis of the corpus callosum). The corpus callosum is the tissue connecting the left and right halves of the brain. Results found in an MRI may lead to checking glycine levels and genetic testing.

Severity at Diagnosis

When diagnosed, often NKH is given a category: ‘severe’ or ‘attenuated’. You may hear these words used in a medical context. It may be useful to know that severity is difficult to diagnose accurately in the neonatal period. This is because both severe and attenuated variants can look similar at this stage, so you may not get a diagnosis of how ‘severe’ or ‘attenuated’ your child’s NKH is right away.

Sometimes medical professionals might use certain factors to help define severity, such as:

• The age when symptoms appear.
• Ratio of glycine levels in blood and cerebrospinal fluid (this is the fluid which surrounds the brain).
• MRI imaging showing abnormal brain structure (such as a smaller/thinner Corpus Callosum, which is the tissue connecting
  the right and left halves of the brain).
• Molecular genetic testing.

Over time (from age two onwards), ongoing developmental progress (defined by a Developmental Quotient (DQ) score) might
be used to understand whether a variant is severe or attenuated.

Genetic confirmation can sometimes be used to understand the likelihood of a severe or attenuated outcome. This is why identifying the specific mutations responsible can be helpful. While some mutations are associated with a type of severity, many mutations are unknown.

Knowledge about the specific genetic mutations can also be helpful in future pregnancies of the parents. If this is something you would like to learn more about, we have included more information in the ‘Living with NKH’ section.