Tummolo Albina, Melpignano Livio, Carella Antonella, Di Mauro Anna Maria, Piccinno Elvira, Vendemiale Marcella, Ortolani Federica, Fedele Stefania, Masciopinto Maristella, Papadia Francesco
Metabolic Diseases and Clinical Genetics Unit, Children's Hospital Giovanni XXIII, Via Amendola 207, 70126, Bari, Italy.
J Med Case Rep. 2018 Apr 22;12(1):103. doi: 10.1186/s13256-018-1631-1.
Propionic acidemia is a rare autosomal recessive inherited metabolic disorder that can inhibit the synthesis of N-acetylglutamate, the obligatory activator in urea synthesis, leading to hyperammonemia. N-carbamylglutamate ameliorates hyperammonemia in decompensated propionic acidemia. The effects of long-term continuous N-acetylglutamate administration in such patients are unknown. We report our clinical experience with continuous administration of N-acetylglutamate for 6 years in a patient with propionic acidemia frequently presenting with hyperammonemia.
A male Caucasian patient with frequently decompensated propionic acidemia and hyperammonemia was admitted 78 times for acute attacks during the first 9 years of his life. Continuous daily treatment with oral N-carbamylglutamate 100 mg/kg (50 mg/kg after 6 months) was initiated. During 6 years of treatment, he had a significant decrease in his mean plasma ammonia levels (75.7 μmol/L vs. 140.3 μmol/L before N-carbamylglutamate therapy, p < 0.005 [normal range 50-80 μmol/L]) and fewer acute episodes (two in 6 years).
Our results suggest a benefit of N-acetylglutamate administration outside the emergency setting. If this observation is confirmed, future studies should aim to optimize the dosage and explore effects of the dosage requirements on other drugs and on protein tolerance.
丙酸血症是一种罕见的常染色体隐性遗传代谢紊乱疾病，可抑制N - 乙酰谷氨酸的合成，而N - 乙酰谷氨酸是尿素合成中的必需激活剂，会导致高氨血症。N - 氨甲酰谷氨酸可改善失代偿性丙酸血症中的高氨血症。长期持续给予N - 乙酰谷氨酸对此类患者的影响尚不清楚。我们报告了对一名频繁出现高氨血症的丙酸血症患者持续给予N - 乙酰谷氨酸6年的临床经验。
一名患有频繁失代偿性丙酸血症和高氨血症的白种男性患者，在其生命的前9年因急性发作入院78次。开始每天口服100mg/kg的N - 氨甲酰谷氨酸进行持续治疗（6个月后为50mg/kg）。在6年的治疗期间，他的平均血浆氨水平显著下降（从N - 氨甲酰谷氨酸治疗前的140.3μmol/L降至75.7μmol/L，p < 0.005[正常范围50 - 80μmol/L]），急性发作次数减少（6年中2次）。
我们的结果表明在非紧急情况下给予N - 乙酰谷氨酸有益。如果这一观察结果得到证实，未来的研究应旨在优化剂量，并探索剂量需求对其他药物和蛋白质耐受性的影响。
