What else is it called?
- Glycine Encephalopathy
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What causes it?
NKH is a rare, inherited metabolic disorder caused by a problem in the GLDC or AMT gene. These genes are responsible for controlling a group of enzymes that work together to break down an amino acid called glycine. Amino acids are the building blocks of protein. Glycine is used by the body as a neurotransmitter, which sends chemical messages to the brain. A problem in either the GLDC or AMT gene means the group of enzymes do not work properly. This causes glycine to build up in the body’s tissues and organs, especially in the brain and spinal cord, leading to severe problems.
There are different forms of NKH. The most common form is known as the classical type. Other forms have varying ages of onset, and varying signs and symptoms. Most cases are caused by a problem in the GLDC gene. Only 10 -15% of cases are caused by a problem in the AMT gene. There are a small number of cases where the cause is unknown. If you have tests which show your enzymes are not breaking down glycine properly, but you do not have any problems with the GLDC or AMT genes, you have variant NKH. There are many different genes which may cause this.
How common is it?
We do not know exactly how common this disorder is. It is thought to affect around 1 person in every 76,000. There have only been a few studies relating to prevalence. These have shown that NKH affects approximately 1 in 55,000 newborns in Finland and about 1 in 63,000 newborns in British Columbia, Canada.
What are the signs and symptoms?
The classical type appears shortly after birth. Babies may have the following symptoms:
▪ feeding difficulties
▪ appear floppy due to low muscle tone (hypotonia)
▪ abnormal jerky and writhing movements
▪ breathing problems (apnoea) requiring a ventilator.
Some children no not survive this neonatal period, and parents will need to work with doctors to agree an end of life care plan and ensure full support for the family. This often results in withdrawing from intensive care and life support.
Children who do survive will develop severe learning difficulties and they will have delay in the development of thought processes and movement (psychomotor development). Often children do not develop beyond the capabilities expected of a 6-week-old. Seizures develop which are progressive and difficult to manage. Symptoms affecting the bones and skeletal muscle may cause problems. They may develop a movement disorder causing involuntary twitching or writhing (choreoathetosis). Feeding becomes progressively difficult requiring intervention. Breathing problems become progressively severe and increasingly difficult to manage and this is often the cause of death.
As mentioned above, there are other forms of NKH. The most common is the infantile form. In this form, you may not notice any problems until your baby is about 6 months old. At this age your baby may not reach their expected developmental milestones and begin to have seizures. Developmental delays can range from mild to profound. With age, the following symptoms develop:
- learning difficulties
- intellectual disability
- abnormal movements
- ADHD (Attention Deficit Hyperactive Disorder
- behavioral problems including:
Knowledge and understanding about NKH is increasing rapidly. The effects of the disorder can depend on which gene is affected and the specific problem within the gene.
Other symptoms can include:
- muscle contraction or muscle stiffness
- balance problems
- sight problems due to the optic nerve.
- problems with the white matter of the brain
- heart problems
- increased resistance to blood flow in the lungs
- a build-up of acid in the blood
How is it diagnosed?
NKH can be diagnosed by:
- Measuring the levels of glycine in the blood and fluid surrounding the brain and spinal cord (Cerebral spinal fluid/CSF) ¨
- Molecular analysis
- Brain MRI imaging
Prenatal diagnosis is available if there is a family history of the disorder.
Can it be treated?
There is no cure for NKH. Any treatment given aims to provide relief for the symptoms that are present and to ensure the highest level of support and care for your child and for your family.
Medications used in the management of this condition may include:
- Sodium benzoate – reduces glycine levels, reduces seizures and improves alertness. Requires close monitoring.
- Dextromethorphan – reduce seizures and improve alertness and jerky movements. If treated early together with benzoate, can improve development and seizures.
- Anticonvulsants – to manage seizures. Management is difficult. Avoid valproate. Vigabitrin carries a high risk of adverse reaction.
Management of this condition and help looking after a child with NKH will require the input and support from a multidisciplinary team of professionals working together including doctors, nurses, physiotherapists, sensory specialists, dietitans, and speech and language therapists. Support from Continuing Care Nursing Teams, a Children’s Hospice and Community Palliative Care teams and a strong support network is recommended.
Do my family need to be tested?
NKH can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. If the child only inherits one copy of the faulty gene, they’ll be a carrier of the condition but won’t have the condition.
If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.
If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.
Once you are diagnosed, you can speak to a genetic counsellor. They can explain how NKH is inherited. They can also tell you about genetic testing for the rest of your family.
References are available on request.