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Hyperammonaemia due to NAGS, IVA, MMA or PA

NAGS deficiency

N-aceteylglutamate synthase (NAGS) deficiency is a very rare disorder and is known as the rarest of the urea cycle disorders (UCD). Urea cycle disorders are inherited conditions in which the body lacks, or is deficient in, one of the six enzymes needed to transform ammonia into a compound called urea and pass it out of the body into urine. If an enzyme is faulty, nitrogen (a waste product of protein metabolism) accumulates in the form of ammonia, a highly toxic substance. This results in hyperammonaemia (elevated blood ammonia).

 
Organic acidaemias (IVA, MMA or PA)

An 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 to another.

If an enzyme is faulty it results in the build-up of harmful products before the block, much in the same way that traffic builds up when there is a hold up on a busy road. In organic acidaemias, one of the enzymes is not functioning properly. The organic acids that build up before the block in the pathway give the name to each condition:

  • Propionic acid – propionic acidaemia (PA)
  • Methylmalonic acid – methylmalonic acidaemia (MMA)
  • Isovaleric acid – isovaleric acidaemia (IVA).

Symptoms include hyperammonemia and vary from person to person, and may present at different ages.

Babies with hyperammonaemia due to NAGS deficiency or PA, MMA and IVA can become very unwell during the first weeks of life. They usually present with drowsiness, rapid breathing and vomiting and can become seriously ill.

Older children may become very ill, having had a healthy childhood with no sickness before this deterioration. This so-called 'decompensation' may be brought about by an illness such as a cold. Sometimes a sudden increase in the amount of protein eaten eg. while on holiday or following a celebration, may also precipitate these types of symptoms.

There is also a group of older patients, often teenagers, which present with crhonic episodes of vomiting and drowsiness. They may be considered to have a milder variation of the condition; however careful management is just as important.

With proper drug therapy, the progression of the condition can be halted or symptoms reduced.

 

Recordati Rare Diseases is supporting the European Registry and Network for Intoxication Type Metabolic Disorders (E-IMD) in the development of information for patients and families. Information on NAGS deficiency and the organic acidaemias is available in several languages, visit www.e-imd.org.