Treacy E, Clow C L, Reade T R, Chitayat D, Mamer O A, Scriver C R
DeBelle Laboratory for Biochemical Genetics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
J Inherit Metab Dis. 1992;15(1):121-35. doi: 10.1007/BF01800354.
Four patients with classical maple syrup urine disease were treated for up to 5885 days per patient with a relaxed protocol allowing branched-chain amino acid levels in plasma to rise about 5 times the normal mean value. The patients have had satisfactory development and lifestyle. They spent 318 days in hospital during 19,937 aggregate treatment days. Plasma levels of leucine and the corresponding 2-oxo acid were shown to be elevated disproportionately relative to the other branched-chain metabolites. Levels of isoleucine and valine were lower than those of leucine apparently because of runout into alternative metabolite pools, namely the R metabolites for isoleucine and the hydroxyacid for valine. The chronic accumulation of branched-chain 2-oxo acid(s) in our patients was associated with chronic dysmyelinating changes in CNS visible by imaging. Another patient with a thiamine-responsive variant of maple syrup urine disease had five acute crises incurring 29 days in hospital in a total of 6910 treatment days. However, she did not have chronic metabolic dyshomeostasis (her average plasma amino acid values were normal) and she had no evidence of dysmyelination. A relaxed treatment protocol for patients with maple syrup urine disease may benefit them in quality of life, but it apparently exacts a cost in metabolic control and CNS pathology.
4例经典型枫糖尿症患者采用宽松方案治疗，每位患者最长治疗5885天，该方案允许血浆中支链氨基酸水平升高至正常平均值的约5倍。患者发育良好，生活方式正常。在总计19937个治疗日中，他们住院318天。结果显示，亮氨酸及其相应的2-氧代酸的血浆水平相对于其他支链代谢产物升高得不成比例。异亮氨酸和缬氨酸的水平低于亮氨酸，这显然是因为它们进入了替代代谢产物池，即异亮氨酸的R代谢产物池和缬氨酸的羟酸池。我们的患者中支链2-氧代酸的慢性蓄积与影像学可见的中枢神经系统慢性脱髓鞘改变有关。另1例硫胺素反应性变异型枫糖尿症患者在总共6910个治疗日中有5次急性发作，住院29天。然而，她没有慢性代谢失调（她的平均血浆氨基酸值正常），也没有脱髓鞘的证据。枫糖尿症患者采用宽松治疗方案可能会改善其生活质量，但显然在代谢控制和中枢神经系统病理方面要付出代价。
