N-acetylglutamate synthetase deficiency (NAGS deficiency) is a very rare autosomal recessive disorder of the urea cycle and causes hyperammonaemia. The reason for this is mutations in the NAGS gene, which leads to the defective formation of N-acetylglutamate, which is an important enzyme activator in the urea cycle.
The consequence of this is a disruption of nitrogen excretion, which leads to the accumulation of highly neurotoxic ammonia in the blood. Alternatively, NAGS deficiency may also occur as a result of metabolic disorders of the fatty acids or in treatments with valproic acid.
Severe forms of NAGS show initial symptoms such as refusal of food intake, vomiting, diarrhea, respiratory problems, and progressive lethargy at 24-72 hours postpartum. This causes cramps, ataxia, hyperreflexia and cerebral edema. Left untreated, the lethargy can turn into a deadly coma.
Brain damage causes developmental delays and mental retardation in the longer term. In addition to severely affected forms, there are also lighter forms that show symptoms only after adulthood in adulthood, but these patients may also suffer from lethargy and coma.
With early start of therapy, the prognosis of the patients is good, the psychomotor development is normal. Due to the potentially fatal coma and the neurological damage, the prognosis for untreated patients is poor.
The incidence of NAGS is unknown, with only a few cases known worldwide. Because of this low incidence, the disease is often not properly diagnosed.