Ristoff E, Burstedt M, Larsson A, Wachtmeister L
Department of Pediatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
J Inherit Metab Dis. 2007 Feb;30(1):102. doi: 10.1007/s10545-006-0412-y. Epub 2007 Jan 5.
We report the ophthalmological findings of two sisters with severe glutathione synthetase deficiency, an autosomal recessive inborn error of metabolism resulting in very low intracellular levels of the free-radical scavenger glutathione. The patients were investigated because of declining visual acuity. The most prominent finding was progressive retinal dystrophy with hyperpigmentations and maculopathy. Generally disturbed functioning of both the outer and inner layers of the retina resulted in attenuated or nearly abolished electroretinograms. These findings agree with a rod/cone type of retinal dystrophy, and we suggest that this is due to glutathione deficiency. Treatment with antioxidants such as vitamins E and C seems to prevent the progression of CNS damage. We speculate that it might also prevent retinal dystrophy in patients with glutathione synthetase deficiency. We suggest that patients with retinal dystrophy and additional neurological signs should be investigated for a defect in glutathione metabolism. Also, we recommend that patients with low levels of glutathione should be examined for retinal dystrophy. Our results suggest that a decreased capacity for scavenging reactive oxygen species and/or increased oxidative stress may cause retinal dystrophy. If this is the case, the redox state in the retina should be a potentially useful therapeutic target to prevent reduced visual function and blindness.
我们报告了两名患有严重谷胱甘肽合成酶缺乏症姐妹的眼科检查结果,这是一种常染色体隐性遗传的先天性代谢缺陷,会导致细胞内自由基清除剂谷胱甘肽水平极低。这两名患者因视力下降接受检查。最显著的发现是进行性视网膜营养不良伴色素沉着过多和黄斑病变。视网膜外层和内层的功能普遍紊乱导致视网膜电图减弱或几乎消失。这些发现与视杆/视锥型视网膜营养不良相符,我们认为这是由于谷胱甘肽缺乏所致。用维生素E和C等抗氧化剂治疗似乎可预防中枢神经系统损伤的进展。我们推测它也可能预防谷胱甘肽合成酶缺乏症患者的视网膜营养不良。我们建议,对于患有视网膜营养不良及其他神经学体征的患者,应检查其谷胱甘肽代谢缺陷情况。此外,我们建议对谷胱甘肽水平低的患者进行视网膜营养不良检查。我们的结果表明,清除活性氧的能力下降和/或氧化应激增加可能导致视网膜营养不良。如果是这样,视网膜的氧化还原状态应该是预防视力下降和失明的一个潜在有用的治疗靶点。