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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.

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.

Because glycine is not broken down, it accumulates in the body. Glycine is an important molecule in the brain and has various functions, such as transmitting signals from one brain cell to another. Toxic levels glycine disrupts the function of the brain causing brain damage.

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. Unfortunately, most born with NKH have limited life spans.

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. Canada drug superstore coupon code.

The Glycine Cleavage System

The glycine cleavage system (GCS, also known as the glycine decarboxylase complex or GDC) is how our bodies process glycine. 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 Nexpro 20 mg price

Glycine Toxicity

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. It’s these symptoms that cause NKH.

Symptoms

There are a range of different symptoms that are unique to each child (due to their unique mutation).  Typically, most children will experience some form of seizures, cognitive delay and muscle/movement disorders. A list of typical symptoms and their severity are as follows:

Glycine
100% of patients likely to experience symptoms.

  • Hyperglycinemia – 100%

Cognitive Disorders
81% of patients have been recorded with one or more of these symptoms.

  • Profound mental retardation (PMR)
  • Cognitive Impairment
  • Speech Delay
  • ADHD
  • Aggressive Behaviour
  • Hyperactivity
  • Hypoactivity
  • Sexual impulsivity
  • Stranger anxiety
  • Autism
  • Delerium

Seizure Disorders
72% of patients have been recorded with one or more of these symptoms.

  • Intractable Seizures
  • Irregular EEG
  • Epilepsy
  • Multifocal clonus
  • Myoclonic Seizures
  • Hiccups
  • Eye Deviation
  • Automatism

Muscle/Movement Control Disorders
35% of patients have been recorded with one or more of these symptoms.

  • Brisk reflexes and clonus
  • Flexor spasms
  • Spasticity
  • Hypotonia
  • Poor suck/failure to feed
  • Weak cry
  • Lethargy
  • Global developmental delay
  • Reduced deep tendon reflexes
  • Inability to walk
  • Ataxia
  • Choreoathetosis
  • Dysdiadochokinesia
  • Psychomotor delay
  • Severe spastic diplegia
  • Hemiparesis

Brain Malformations/
32% of patients have been recorded with one or more of these symptoms.

  • Coma
  • Hypoplasia of corpus callosum
  • Thin corpus callosum

Treatment

There is no known cure for NKH, but there are two medications which can help improve quality of life.  Sodium Benzoate can normalise the levels of glycine in the blood, and reduce levels of glycine in the brain/spinal fluid. More about Sodium Benzoate here.

Dextromethorphan can block the brain receptors which often overfire due to increased levels of glycine. By temporarily giving them a break, it slows neurone death, which is important (particularly in the first two years when your babies brain is growing exponentially) for long term outcome.  More about dextromethorphan here.

It’s important your child takes these two medications as soon as possible. This study (Source) recruited four sibling pairs who had attenuated NKH. It was found that the younger sibling, who was treated with SB and DXM much earlier than their older sibling hit more developmental milestones and had a higher developmental quotient . There was also a difference in seizure frequency and the adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication.

Typically a treatment package will be built around your child to manage symptoms. This might include antiepileptics, intense therapy (such as physio, occupational therapy, speech and language therapy etc) and other medications.

For more about NKH, please visit www.foundationnkh.org