Rare Disease

N-acetylglutamate synthetase (NAGS) deficiency : overview

  • May 16, 2023
  • 2 mins read

N-acetyl glutamate synthase (NAGS) deficiency is a rare genetic disorder in which ammonia levels in the blood are unusually high. Ammonia, generated in the body when proteins are broken down, is poisonous if the quantities grow too high. Excess ammonia has a particularly strong effect on the brain. It is a rare genetic condition characterized by the total or partial absence of the enzyme NAGS.
NAGS is one of six enzymes that participate in the urea cycle, which breaks down and removes nitrogen from the body. The absence of the NAGS enzyme causes an excessive buildup of nitrogen in the blood in the form of ammonia. Excess ammonia, a neurotoxic, passes through the blood to the central nervous system, causing the symptoms and clinical findings of NAGS deficiency. Vomiting, reluctance to eat, gradual lethargy, and coma are all symptoms. NAGS deficiency is passed down through families as an autosomal recessive condition.

NAGS insufficiency frequently manifests in the first few days of life. An infant with this illness may be tired (lethargic) or unwilling to eat and struggle to regulate their respiratory rate or body temperature. Babies severely afflicted may have convulsions, odd bodily movements, or fall into a coma. Developmental delay and intellectual disability are possible consequences of N-acetyl glutamate synthase deficiency.
Signs and symptoms of N-acetyl glutamate synthase deficiency do not develop until later in life in some affected persons. Some persons with this type of disorder realize that consuming high-protein meals, such as meat, impacts how they feel, but they may not understand why. Illness or other stress can cause vomiting, lack of coordination, headaches, confusion, behavioral abnormalities, or coma in many affected persons.

Mutations in the NAGS gene cause N-acetyl glutamate synthase insufficiency. Because difficulties with the urea cycle cause it, this condition belongs to a group of hereditary diseases known as urea cycle disorders. The urea cycle is a series of events that take place in liver cells. This cycle breaks down excess nitrogen produced by the body when protein is utilized to produce urea. Urine excretes urea from the body.

NAGS deficient treatment aims to avoid excessive ammonia formation or to remove excess ammonia during a hyperammonemic crisis. Long-term treatment for NAGS deficiency included dietary limitations and stimulation of alternate nitrogen conversion and excretion mechanisms (alternative pathways therapy).
Carbaglu tablets (carbamylglutamate) were licensed by the US Food and Drug Administration (FDA) in 2010 to lower blood ammonia levels in patients with NAGS deficiency. Recordati Rare Diseases manufactures Carbaglu. Some people who take carbamoyl glutamic acid may still need to follow dietary restrictions and take arginine supplements.