- NAGS deficiency is a rare genetic metabolic disorder characterized by a deficiency of the enzyme N-acetylglutamate synthetase.
- This enzyme plays a critical role in the urea cycle, a process essential for removing nitrogenous waste (ammonia) from the bloodstream.
Pathophysiology
- NAGS deficiency is caused by genetic variants (mutations) in the NAGS gene, located on chromosome 17q21.31.
- The enzyme N-acetylglutamate synthetase (NAGS) catalyzes the synthesis of N-acetylglutamate (NAG), a crucial activator of carbamoyl phosphate synthetase 1 (CPS1).
- CPS1 is the first and rate-limiting enzyme in the urea cycle, initiating the conversion of ammonia to urea.
- A deficiency in NAGS impairs CPS1 activation, resulting in:
- Accumulation of ammonia in the bloodstream (hyperammonemia).
- Subsequent toxic effects primarily targeting the central nervous system (CNS).
Signs & Symptoms of NAGS Deficiency
- NAGS deficiency can result from either a complete or partial absence of the N-acetylglutamate synthetase enzyme.
- Clinical presentation varies significantly, depending on the severity of enzyme deficiency:
- Severe form (complete enzyme deficiency) typically presents shortly after birth.
- Milder form (partial enzyme deficiency) may present later during infancy, childhood, or adulthood.
Severe Form (Complete NAGS Enzyme Deficiency)
- Symptoms typically emerge within 24-72 hours after birth and may include:
- Refusal to eat or poor feeding habits
- Progressive lethargy (extreme tiredness)
- Recurrent vomiting
- Diarrhea
- Irritability
- Enlarged liver (hepatomegaly)
Login to Read More
