Metabolic Unit, Department of Clinical Chemistry, VU Medical Center, Amsterdam, Netherlands.
Pediatrics. 2012 Dec;130(6):e1716-9. doi: 10.1542/peds.2012-1094. Epub 2012 Nov 12.
α-Amino adipic semialdehyde (α-AASA) accumulates in body fluids from patients with pyridoxine-dependent epilepsy because of mutations in antiquitin (ALDH7A1) and serves as the biomarker for this condition. We have recently found that the urinary excretion of α-AASA was also increased in molybdenum cofactor and sulfite oxidase deficiencies. The seizures in pyridoxine-dependent epilepsy are caused by lowered cerebral levels of pyridoxal-5-phosphate (PLP), the bioactive form of pyridoxine (vitamin B(6)), which can be corrected by the supplementation of pyridoxine. The nonenzymatic trapping of PLP by the cyclic form of α-AASA is causative for the lowered cerebral PLP levels. We describe 2 siblings with clinically evident pyridoxine-responsive seizures associated with increased urinary excretion of α-AASA. Subsequent metabolic investigations revealed several metabolic abnormities, all indicative for molybdenum cofactor deficiency. Molecular investigations indeed revealed a known homozygous mutation in the MOCS2 gene. Based upon the clinically evident pyridoxine-responsive seizures in these 2 siblings, we recommend considering pyridoxine supplementation to patients affected with molybdenum cofactor or sulfite oxidase deficiencies.
α-氨基己二酸半醛（α-AASA）在吡哆醇依赖性癫痫患者的体液中积累，因为 antiquitin（ALDH7A1）的突变，并作为这种情况的生物标志物。我们最近发现，在钼辅因子和亚硫酸盐氧化酶缺乏症中，α-AASA 的尿排泄也增加了。吡哆醇依赖性癫痫的癫痫发作是由脑中吡哆醇-5-磷酸（PLP）水平降低引起的，PLP 是吡哆醇（维生素 B（6））的生物活性形式，可通过补充吡哆醇来纠正。PLP 被α-AASA 的环状形式非酶捕获是导致脑中 PLP 水平降低的原因。我们描述了 2 名具有明显临床吡哆醇反应性癫痫发作的同胞，伴有α-AASA 尿排泄增加。随后的代谢研究显示出几种代谢异常，均提示钼辅因子缺乏。分子研究确实揭示了 MOCS2 基因的一个已知纯合突变。基于这 2 名同胞中明显的临床吡哆醇反应性癫痫发作，我们建议考虑向受钼辅因子或亚硫酸盐氧化酶缺乏影响的患者补充吡哆醇。
