How is N-Acetylglutamate Synthetase Deficiency diagnosed?

N-Acetylglutamate Synthetase Deficiency Diagnosis

N-Acetylglutamate synthetase deficiency (NAGS deficiency) is a rare genetic disorder that affects the urea cycle, a process responsible for removing toxic ammonia from the body. Early diagnosis of NAGS deficiency is crucial to prevent severe complications and initiate appropriate treatment.

1. Clinical Evaluation:

The diagnosis of NAGS deficiency begins with a thorough clinical evaluation. The healthcare provider will review the patient's medical history, symptoms, and family history of similar conditions. Symptoms of NAGS deficiency may include poor feeding, vomiting, lethargy, seizures, and developmental delays.

2. Laboratory Tests:

Several laboratory tests are used to diagnose NAGS deficiency:

• Plasma Ammonia Levels: Elevated levels of ammonia in the blood are a key indicator of urea cycle disorders, including NAGS deficiency.


• Plasma Amino Acid Analysis: This test measures the levels of various amino acids in the blood. NAGS deficiency is characterized by low levels of N-acetylglutamate (NAG), which is necessary for the proper functioning of the urea cycle.


• Urine Organic Acid Analysis: This test helps identify abnormal metabolites that may be present in individuals with NAGS deficiency.

3. Genetic Testing:

Genetic testing plays a crucial role in confirming the diagnosis of NAGS deficiency. It involves analyzing the patient's DNA for mutations or changes in the NAGS gene. This test can identify specific genetic variants responsible for the deficiency.

4. Enzyme Activity Assay:

In some cases, an enzyme activity assay may be performed to measure the activity of N-acetylglutamate synthetase directly. This test helps determine the functionality of the enzyme and confirm the diagnosis of NAGS deficiency.

5. Newborn Screening:

In certain regions, NAGS deficiency may be included in newborn screening programs. This involves testing a small blood sample from newborns to detect the presence of elevated ammonia levels or abnormal amino acid profiles, allowing for early diagnosis and intervention.

Early diagnosis of N-Acetylglutamate Synthetase Deficiency is essential to prevent life-threatening complications. A multidisciplinary approach involving clinical evaluation, laboratory tests, genetic testing, and newborn screening can aid in the accurate diagnosis of this rare genetic disorder.