Differential Diagnosis for Severe Hyperammonemia, Elevated Glutamine, and Low Citrulline
Single Most Likely Diagnosis
- Carbamoyl Phosphate Synthetase I (CPS I) Deficiency: This enzyme plays a crucial role in the urea cycle, converting ammonia into carbamoyl phosphate. A deficiency leads to severe hyperammonemia, as seen in the patient. Elevated glutamine is a result of the body attempting to detoxify ammonia by converting it into glutamine. Low citrulline levels are consistent with CPS I deficiency, as citrulline production is impaired due to the lack of carbamoyl phosphate.
Other Likely Diagnoses
- Ornithine Transcarbamylase (OTC) Deficiency: Another key enzyme in the urea cycle, OTC deficiency can also lead to hyperammonemia and elevated glutamine. However, citrulline levels are typically low or undetectable, making it a plausible diagnosis given the patient's low citrulline levels.
- N-Acetylglutamate Synthase (NAGS) Deficiency: This enzyme is necessary for the production of N-acetylglutamate, an essential activator of CPS I. A deficiency in NAGS can mimic CPS I deficiency, leading to similar biochemical abnormalities, including severe hyperammonemia, elevated glutamine, and low citrulline.
Do Not Miss Diagnoses
- Argininosuccinate Synthetase (ASS) Deficiency (Citrullinemia): Although citrulline levels are typically elevated in ASS deficiency, there can be instances where citrulline is low, especially in the neonatal period or due to secondary inhibition of the enzyme. Missing this diagnosis could be fatal due to the potential for severe hyperammonemia.
- Argininosuccinate Lyase (ASL) Deficiency (Argininosuccinic Aciduria): Similar to ASS deficiency, ASL deficiency can present with variable citrulline levels. It is crucial not to miss this diagnosis due to the risk of severe hyperammonemia and its associated complications.
Rare Diagnoses
- Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) Syndrome: A rare disorder characterized by elevated ornithine, ammonia, and homocitrulline in the blood. While citrulline levels might not directly point to this diagnosis, the combination of hyperammonemia and elevated glutamine could warrant consideration of HHH syndrome in the differential diagnosis.
- Pyruvate Carboxylase Deficiency: Although primarily associated with disorders of energy metabolism, severe forms of pyruvate carboxylase deficiency can lead to hyperammonemia. The biochemical profile might not directly suggest this diagnosis, but it remains a rare consideration in the context of severe hyperammonemia and metabolic derangements.