WHAT IS HYPERGLYCINEMIA?

KETOTIC?

Nonketotic hyperglycinemia is an inborn error of glycine metabolism causing an accumulation of this amino acid in blood, urine and brain. is known also as hyperglycinemic encephalopathy, due to serious disorder that causes the accumulation of glycine in the brain (brain).

WHAT IS GLYCINE?

Glycine is the simplest and most abundant amino acid. It is part of proteins (chains of amino acids). It is not essential in the human diet, since we can form it from other compounds, especially another amino acid, serine.

HOW IS GLYCINE METABOLIZED?

Glycine is formed from serine by a significant reversible reaction. Glycine is degraded by an enzyme complex mitochondrial located in brain, kidney, liver and placenta, which is made up of 4 proteins (P, H, T and L): the glycine degradation system (GCS). in these reactions produce methyl groups (C1) that can be yield to other compounds, so this reaction It is of great metabolic importance.

WHAT FUNCTIONS DOES GLYCINE HAVE?
In addition to being a precursor to multiple compounds, Glycine is a brain neurotransmitter.

WHAT IS A NEUROTRANSMITTER?
Neurotransmitters are chemical messengers that release neurons to communicate with each other. Some neurotransmitters trigger the onset of activity of the neurons that “receive” them (excitatory neurotransmitters), while others inhibit that activity (inhibitory neurotransmitters).

Glycine has a double function: on the one hand it is a inhibitory neurotransmitter, acting on some specific receptors in the brainstem and spinal cord. On the other hand, it is an excitotoxic neurotransmitter, which acts by modulating the N-methyl-D-aspartate receptor (NMDA) in the cerebral cortex.

This NMDA receptor is actively involved in the development of the nervous system, brain plasticity and also in degenerative processes.

WHAT DOES AN ERROR MEAN? METABOLIC?

When there is an alteration (error) in the metabolism (set of enzymatic reactions that allow the life), some metabolic process does not occur with the due effectiveness and this can cause the accumulation of some compound that is toxic to our body, like glycine, which is neurotoxic. These alterations have pathological consequences.

WHAT HAPPENS IN HYPERGLYCINEMIA NON-KETOTIC?

Nonketotic hyperglycinemia can be caused by defect in one of the four enzymes involved in its degradation forming the GCS complex.

WHY DOES A DEFICIENCY OCCUR? OF GCS ACTIVITY?

Each of the metabolic reactions that will give rise to the compounds that make up our body it is genetically determined (encoded). All we inherit from our parents the correct information or altered that determines that each of these is carried out metabolism processes. GCS deficiency occurs due to mutations (stable and inherited changes) in one of the 4 genes encoding the enzymes that form the complex. I know inherited in an autosomal recessive manner, that is, parents are carriers of mutations in one of these genes, although they do not suffer the effects of the deficiency. Yes both parents pass on a mutation to the child, the child You will experience nonketotic hyperglycinemia.

WHAT HAPPENS IN THE CASE OF A CHILD WHO IS BORN WITH HYPERGLYCINEMIA NON-KETOTIC?

The first manifestations may occur at birth birth or in the first weeks of life, although the neurological damage may have already started intrauterine. The consequences of the inhibitory effect of glycine are hypotonia, apnea crisis, hiccups, increased of the tendon reflexes. As a consequence of its excitotoxic role appear convulsions, delayed mental and brain development disorders. Usually the course of the disease is rapid, although there are exceptions.

WHAT ARE THE POSSIBILITIES THERAPEUTICS IN HYPERGLYCINEMIA NON-KETOTIC?

The patient must be diagnosed and treated as as early as possible. Diagnosis is based on analysis amino acids in plasma and cerebrospinal fluid patient to quantify the increase in glycine and assess the relationship between the concentrations of this amino acid in cerebrospinal fluid and plasma.

Treatment of nonketotic hyperglycinemia is based on:
a) In protein restriction,
b) Removal of glycine by using benzoate oral sodium,
c) Vitamins (folic acid and pyridoxine to stimulate the GPS complex) and
d) Dextromethorphan, to limit excitotoxicity.

Nonketotic hyperglycinemia is a disease that carries serious consequences. The early diagnosis and symptomatic treatment can improve the comfort of these patients.