Gregg A R, Warman A W, Thorburn D R, O'Brien W E
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
J Inherit Metab Dis. 1998 Jun;21(4):382-90. doi: 10.1023/a:1005302607897.
We identified a patient who excreted large amounts of methylmalonic acid and malonic acid. In contrast to other patients who have been described with combined methylmalonic and malonic aciduria, our patient excreted much larger amounts of methylmalonic acid than malonic acid. Since most previous patients with this biochemical phenotype have been reported to have deficiency of malonyl-CoA decarboxylase, we assayed malonyl-CoA decarboxylase activity in skin fibroblasts derived from our patient and found the enzyme activity to be normal. We examined four isocaloric (2000 kcal/day) dietary regimes administered serially over a period of 12 days with 3 days devoted to each dietary regimen. These diets were high in carbohydrate, fat or protein, or enriched with medium-chain triglycerides. Diet-induced changes in malonic and methylmalonic acid excretion became evident 24-36 h after initiating a new diet. Total excretion of malonic and methylmalonic acid was greater (p < 0.01) during a high-protein diet than during a high-carbohydrate or high-fat diet. A high-carbohydrate, low-protein diet was associated with the lowest levels of malonic and methylmalonic acid excretion. Perturbations in these metabolites were most marked at night. On all dietary regimes, our patient excreted 3-10 times more methylmalonic acid than malonic acid, a reversal of the ratios reported in patients with malonyl-CoA decarboxylase deficiency. Our data support a previous observation that combined malonic and methylmalonic aciduria has aetiologies other than malonyl-CoA decarboxylase deficiency. The malonic acid to methylmalonic acid ratio in response to dietary intervention may be useful in identifying a subgroup of patients with normal enzyme activity.
我们发现了一名排泄大量甲基丙二酸和丙二酸的患者。与其他已报道的合并甲基丙二酸尿症和丙二酸尿症的患者不同，我们的患者排泄的甲基丙二酸量远多于丙二酸。由于之前报道的大多数具有这种生化表型的患者都存在丙二酰辅酶A脱羧酶缺乏，我们检测了来自该患者的皮肤成纤维细胞中的丙二酰辅酶A脱羧酶活性，发现该酶活性正常。我们研究了在12天内连续给予的四种等热量（2000千卡/天）饮食方案，每种饮食方案持续3天。这些饮食分别富含碳水化合物、脂肪或蛋白质，或富含中链甘油三酯。饮食引起的丙二酸和甲基丙二酸排泄变化在开始新饮食后24 - 36小时变得明显。高蛋白饮食期间丙二酸和甲基丙二酸的总排泄量高于高碳水化合物或高脂肪饮食期间（p < 0.01）。高碳水化合物、低蛋白饮食与丙二酸和甲基丙二酸排泄的最低水平相关。这些代谢物的扰动在夜间最为明显。在所有饮食方案中，我们的患者排泄的甲基丙二酸比丙二酸多3 - 10倍，这与丙二酰辅酶A脱羧酶缺乏患者报道的比例相反。我们的数据支持了之前的一项观察结果，即合并丙二酸尿症和甲基丙二酸尿症的病因除了丙二酰辅酶A脱羧酶缺乏外还有其他原因。饮食干预后丙二酸与甲基丙二酸的比例可能有助于识别酶活性正常的患者亚组。
