From the Research
Uridine is the most likely treatment to ease this patient's symptoms. The patient presents with lethargy, weakness, anemia, growth deficiency, elevated orotic acid in urine, and low UMP synthase activity, which are classic signs of orotic aciduria. This rare hereditary metabolic disorder results from deficiency in UMP synthase, a key enzyme in pyrimidine synthesis. Without this enzyme, the body cannot convert orotic acid to uridine monophosphate (UMP), leading to orotic acid accumulation and pyrimidine deficiency. Uridine supplementation provides the end product that the patient cannot synthesize naturally, bypassing the enzymatic defect. This allows normal nucleic acid synthesis to resume, particularly important for rapidly dividing cells like those in the bone marrow and growing tissues. The other nucleosides listed (adenine, guanine, hypoxanthine, and thymidine) would not address the specific pyrimidine deficiency caused by UMP synthase deficiency, as they are either purines or would not convert to the needed uridine compounds.
Key Points
- Orotic aciduria is a rare hereditary metabolic disorder characterized by deficiency in UMP synthase, leading to orotic acid accumulation and pyrimidine deficiency 1, 2, 3, 4, 5.
- The patient's symptoms, including lethargy, weakness, anemia, growth deficiency, and elevated orotic acid in urine, are consistent with orotic aciduria.
- Uridine supplementation has been shown to be effective in treating orotic aciduria by providing the end product that the patient cannot synthesize naturally, thereby bypassing the enzymatic defect 5.
- The most recent study, published in 2021, reports a case of hereditary orotic aciduria with a novel variant in the UMPS gene, which was successfully treated with uridine triacetate 5.
Treatment Recommendation
Based on the evidence, uridine supplementation is the recommended treatment for this patient. This treatment has been shown to be effective in addressing the specific pyrimidine deficiency caused by UMP synthase deficiency, and has been used successfully in recent cases of orotic aciduria 5.