Discover Nonketotic Hyperglycinemia

You will see many descriptions of what Nonketotic Hyperglycinemia (NKH – or glycine encephalopathy) is and how it affects our children. Sadly they all make for pretty hard reading.

However, the experiences of those who treat it and those who live with it are slightly different. As such, we have tried to present you with a balanced view and below are three different descriptions of NKH.

We suggest you read all three and hopefully each will offer you something in terms of understanding what you are dealing with.

What Wikipedia Says

There are several different forms of glycine encephalopathy, which can be distinguished by the age of onset, as well as the types and severity of symptoms. All forms of glycine encephalopathy present with only neurological symptoms, including mental retardation, hypotonia, seizures and brain malformations.

With the classical, or neonatal presentation of glycine encephalopathy, the infant is born after an unremarkable pregnancy, but presents with lethargy, hypotonia, seizures and myoclonic jerks, which can progress to apnea requiring artificial ventilation, and often death. Apneic patients can regain spontaneous respiration in their second to third week of life. After recovery from the initial episode, patients have intractable seizures and profound mental retardation, remaining developmentally delayed.

Some mothers comment retrospectively that they noticed rhythmic hiccuping during pregnancy. Patients with the infantile form of glycine encephalopathy do not show lethargy and coma in the neonatal period, but often have a history of hypotonia. They often have seizures, which can range in severity and responsiveness to treatment, and are typically developmentally delayed.

Glycine encephalopathy can also present as a milder form with episodic seizures, ataxia, movement disorders, and gaze palsy during febrile illness. These patients are also developmentally delayed, to varying degrees. In the later onset form, patients typically have normal intellectual function, but present with spastic diplegia and optic atrophy.

Transient neonatal hyperglycinemia has been described in a very small number of cases. Initially, these patients present with the same symptoms and laboratory results that are seen in the classical presentation. The levels of glycine in plasma and cerebrospinal fluid normalize within eight weeks, and in five of six cases there were no neurological issues at follow-up times up to thirteen years. A single patient was severely retarded at nine months. An immature glycine cleavage system in the brain and liver is suspected as the cause of transient neonatal hyperglicinemia.

What the Experts Say

Nonketotic hyperglycinemia, NKH for short, 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.

What an NKH Family Says

Non-ketotic Hyperglycinemia is a condition where sufferers cannot make an enzyme that is used to metabolise, ie break down, glycine. It is a genetic condition and a genetic defect will have come from each parent. There are some cases where mutations cannot be found in one or both parents but this is very rare.

Glycine is an amino acid and is essential for our bodies to grow and develop.

By not being able to break down glycine and use it as we should, it causes two main problems.

Firstly development, movement, intelligence etc is severely affected as we need glycine for many things like cognitive function, learning and retaining information. As glycine is a neurotransmitter it is also vital in ensuring messages are transmitted correctly from the brain to other parts of the body.

Secondly, because glycine is not broken down and used, toxic levels of it build up in the blood, brain, spinal fluid, organs and tissues. This causes brain damage, seizures which can often be difficult to control, muscle weakness and/or spasticity and a variety of other serious medical issues.

There is no cure for NKH but there are treatments.

Sodium Benzoate (SB) is used to remove the excess glycine from the blood by, in effect, sticking to it, so it is passed out in urine. As SB only lowers levels in the blood, Dextromethorphan is used to dull the part of the brain that glycine aggravates when it is present in brain and spinal fluid. Most children will have at least one seizure medication and nearly all will take some sort of antacid or protein pump inhibitor to protect their stomach against the harsh effect of SB.

You will read many texts on NKH and what it does and all will be pretty depressing reading.

Sadly the mortality rate for children born with this condition is high and many die before they make it out of toddlerhood. Those that survive are often extremely disabled both mentally and physically with uncontrollable seizures. However, what you wont read is about mild cases, moderate cases and the successes and achievements of even the most severe cases. NKH is a devastating and often fatal condition but there are many many variations of it and these children consistently achieve more and live longer than we are led to believe.

A child with NKH has its own agenda and plan.

It wont have read the medical jargon on NKH and it will fight harder than you could ever imagine to simply be part of life. If you are a new parent to an NKH child, no matter what you are told, do not give up until the last. For every child that does exactly what the text books say they will, there is one that doesn’t.

What next?

You are not alone, there are many families and we’re here for you when you’re ready. We’re mostly on Facebook.

In the meantime, there are three main research teams around the world looking at NKH treatments. There are several charities that help fund that research. There are two conferences every year, one in the US and one in the UK. NKH Day is May 2nd. For more about NKH please visit foundationnkh.org

Have hope, hey. Have hope.

Many families choose to direct all well-meaning offers of help towards fundraising for research. Typically Joseph’s Goal in the UK, NKH Crusaders or the Drake Rayden Foundation in the US.