Hyperammonia
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NAGS deficiency
N-aceteylglutamate synthase (NAGS) deficiency is a very rare disorder and is known as the rarest of urea cycle disorders (UCD). Urea cycle disorders are hereditary conditions in which the body lacks, or is deficient in, one of six enzymes needed to convert ammonia into a compound called urea and expel it from the body in the urine. When an enzyme is defective, nitrogen (a waste product of protein metabolism) accumulates in the form of ammonia, a highly toxic substance. This results in hyperammonemia (increased ammonia in the blood).
Organic acidaemias (IVA, MMA or PA).
Organic acidaemia is a genetic disorder caused by a genetic mutation that disrupts normal amino acid metabolism. Amino acids (such as isoloeucine, valine, leucine, lysine and tryptophan) are broken down from the food we eat. Each amino acid has its own pathway that uses a series of enzymes. Each enzyme is essential to convert one substance into another.
When an enzyme is defective, it leads to a buildup of harmful products in front of the block, much the same way traffic builds up when there is a delay on a busy road. In organic acidaemia, one of the enzymes malfunctions. The organic acids that accumulate before the blockage in the route give the name to each condition:
- Propionic acid - propionacidemia (PA)
- Methylmalonic acid - methylmalonacidaemia (MMA)
- Isovaleric acid - isovaleric acid acidemia (IVA).
Symptoms include hyperammonemia and vary from person to person and can occur at different ages.
Babies with hyperammonemia due to NAGS deficiency or PA, MMA and IVA may become very unwell during the first few weeks of life. They usually become drowsy, have rapid breathing and may become seriously ill.
Older children may become very ill, whereas before this deterioration they had a healthy childhood without illness. This so-called "decompensation" can be caused by an illness such as a cold. Sometimes a sudden increase in the amount of protein eaten, such as during the vacations or after a party, can also trigger this type of symptom.
There is also a group of older patients, often teenagers, who present with chronic episodes of vomiting and drowsiness. These patients may be considered milder versions of the condition, but careful treatment is just as important.
With proper drug treatment, the progression of the condition can be stopped or symptoms reduced.
