Crawford T O, Sladky J T, Hurko O, Besner-Johnston A, Kelley R I
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ann Neurol. 1999 Mar;45(3):337-43. doi: 10.1002/1531-8249(199903)45:3<337::aid-ana9>3.0.co;2-u.
Our previous experience with abnormal fatty acid metabolism in several children with spinal muscular atrophy (SMA) prompted evaluation of fatty acid metabolism in a larger cohort. Thirty-three infants with severe infantile SMA were shown to have a significantly increased ratio of dodecanoic to tetradecanoic acid in plasma compared with normal infants and 6 infants affected with equally debilitating, non-SMA denervating disorders. Seventeen children with milder forms of SMA had normal fatty acid profiles. In addition, all 5 infants with severe SMA evaluated in a fasting state developed a distinctive and marked dicarboxylic aciduria, including saturated, unsaturated, and 3-hydroxy forms, comparable in severity with the dicarboxylic aciduria of children with primary defects of mitochondrial fatty acid beta-oxidation. Nine children with chronic SMA and 23 control patients did not develop an abnormal dicarboxylic aciduria during fasting. No known disorder of fatty acid metabolism explains all of the abnormalities we find in SMA. Our data suggest, however, that the abnormalities are not a consequence of SMA-related immobility, systemic illness, muscle denervation, or muscle atrophy. These abnormalities in fatty acid metabolism may be caused by changes in cellular physiology related to the molecular defects of the SMA-pathogenic survival motor neuron gene or neighboring genes.
我们之前对几名脊髓性肌萎缩症（SMA）患儿异常脂肪酸代谢的研究经验促使我们对更大队列的脂肪酸代谢情况进行评估。与正常婴儿以及6名患有同样严重的非SMA去神经疾病的婴儿相比，33名重度婴儿型SMA婴儿的血浆中十二烷酸与十四烷酸的比例显著升高。17名症状较轻的SMA患儿的脂肪酸谱正常。此外，所有5名在禁食状态下接受评估的重度SMA婴儿均出现了独特且明显的二羧酸尿症，包括饱和、不饱和及3 - 羟基形式，其严重程度与线粒体脂肪酸β氧化原发性缺陷患儿的二羧酸尿症相当。9名慢性SMA患儿和23名对照患者在禁食期间未出现异常二羧酸尿症。目前已知的脂肪酸代谢紊乱均无法解释我们在SMA中发现的所有异常情况。然而，我们的数据表明，这些异常并非SMA相关的活动受限、全身性疾病、肌肉去神经支配或肌肉萎缩所致。脂肪酸代谢的这些异常可能是由与SMA致病存活运动神经元基因或邻近基因的分子缺陷相关的细胞生理变化引起的。
