Shimizu N, Yamaguchi S, Orii T
Department of Pediatrics, Gifu University School of Medicine, Japan.
Acta Paediatr Jpn. 1994 Apr;36(2):139-45. doi: 10.1111/j.1442-200x.1994.tb03149.x.
Dicarboxylic aciduria (DCA-uria) is a relatively common finding in the screening of organic acidemias by gas chromatography/mass spectrometry (GC/MS). A considerable number of patients with DCA-uria are involved in disturbances of mitochondrial and peroxisomal fatty acid beta-oxidation. The differential diagnosis of DCA-uria was investigated using a combination of organic acid analysis by GC/MS, carnitine determination, acylcarnitines by fast atom bombardment/mass spectrometry (FAB/MS) and acylglycines by stable-isotope dilution analysis. The relative distribution of urinary metabolites was examined in 46 patients with DCA-uria of different origins, including physiological ketosis of childhood, disorders of propionic acid metabolism, glutaric aciduria type II, Zellweger syndrome and patients who were clinically diagnosed as having Reye syndrome. Zellweger syndrome seemed to be distinguishable from other disorders by the high sebacic acid/adipic acid ratio of DCA-uria and increased excretion of 4-hydroxyphenyllactic acid and 2-hydroxysebacic acid. The mild form of glutaric aciduria type II was often missed by current organic acid analysis alone, but was readily diagnosed by acylcarnitine and acylglycine determination. The ratio of free/total carnitine was low in most of the DCA-uria patients except for two of five cases of Zellweger syndrome and one of three cases of Reye syndrome. The acylcarnitine analysis by FAB/MS showed adipyl-, suberyl-, sebacyl- or dodecanedioylcarnitine as major peaks in most of these patients, although these were not specific. Disease-specific peaks were detectable only in congenital organic acidemias such as glutaric aciduria type II, methylmalonic acidemia and propionic acidemia.
二羧酸尿症（DCA - 尿症）是气相色谱/质谱法（GC/MS）筛查有机酸血症时相对常见的发现。相当一部分患有DCA - 尿症的患者存在线粒体和过氧化物酶体脂肪酸β氧化紊乱。采用GC/MS进行有机酸分析、肉碱测定、快原子轰击/质谱法（FAB/MS）测定酰基肉碱以及稳定同位素稀释分析法测定酰基甘氨酸相结合的方法，对DCA - 尿症进行鉴别诊断。在46例不同病因的DCA - 尿症患者中检测尿代谢物的相对分布，这些病因包括儿童生理性酮症、丙酸代谢紊乱、II型戊二酸尿症、泽尔韦格综合征以及临床诊断为瑞氏综合征的患者。泽尔韦格综合征似乎可通过DCA - 尿症中高含量的癸二酸/己二酸比值以及4 - 羟基苯乳酸和2 - 羟基癸二酸排泄增加与其他疾病相区分。目前仅通过有机酸分析常常会漏诊轻度II型戊二酸尿症，但通过酰基肉碱和酰基甘氨酸测定则很容易诊断。除了5例泽尔韦格综合征患者中的2例以及3例瑞氏综合征患者中的1例，大多数DCA - 尿症患者的游离/总肉碱比值较低。FAB/MS进行的酰基肉碱分析显示，在大多数这些患者中，己二酰 - 、辛二酰 - 、癸二酰 - 或十二烷二酰肉碱为主要峰，尽管这些并不具有特异性。仅在先天性有机酸血症如II型戊二酸尿症、甲基丙二酸血症和丙酸血症中可检测到疾病特异性峰。
