Urinary pyrimidine excretion in arginase deficiency

Area of Science:

• Biochemistry
• Clinical Chemistry
• Metabolic Disorders

Background:

• Urea cycle disorders (UCDs) are genetic conditions affecting nitrogen metabolism.
• Arginase deficiency is a specific UCD impacting arginine breakdown.
• Pyrimidine metabolism can be altered in UCDs, but specific markers for arginase deficiency require further investigation.

Purpose of the Study:

• To investigate urinary pyrimidine excretion patterns in patients with arginase deficiency.
• To assess the utility of urinary pyrimidine measurements for diagnosing and monitoring arginase deficiency.
• To explore the relationship between pyrimidine excretion, protein intake, and arginine levels.

Main Methods:

• High-performance liquid chromatography (HPLC) was employed for the separation and identification of uracil, uridine, pseudouridine, and orotic acid.
• Urine samples from two patients with arginase deficiency (McKusick 20780) were analyzed.
• Pyrimidine levels were correlated with protein intake and urinary arginine excretion.

Main Results:

• Patients exhibited 10-35 times higher than normal urinary uracil excretion.
• Uridine and orotic acid, typically undetectable, were excreted in significant amounts.
• Excretion of uridine and orotic acid correlated with protein intake and urinary arginine levels, while uracil levels remained consistently high.

Conclusions:

• Urinary pyrimidine profiling, particularly elevated uracil, uridine, and orotic acid, is a valuable tool for detecting and differentiating arginase deficiency.
• These measurements can aid in the differential diagnosis of urea cycle disorders.
• Urinary pyrimidine analysis is useful for monitoring dietary management in patients with arginase deficiency.