Carelli V, Barboni P, Zacchini A, Mancini R, Monari L, Cevoli S, Liguori R, Sensi M, Lugaresi E, Montagna P
Institute of Neurology, University of Bologna, Italy.
J Neurol Sci. 1998 Oct 8;160(2):183-8. doi: 10.1016/s0022-510x(98)00239-1.
We report the clinical and genetic study of a Leber's Hereditary Optic Neuropathy (LHON) patient of North African origin harboring the 14484/ND6 mutation of mtDNA. For over a year we followed the ophthalmological course of this 24-year-old male with LHON treated with idebenone and vitamin B12. Serum lactate after effort was evaluated before, during and after therapy. Muscle biopsy was obtained for morphological study. Homo/heteroplasmy of 14484/ND6 mutation was studied in different tissues. Recovery of visual acuity was documented 6 months after onset and 3 months after therapy was established. Baseline serum lactate was elevated but normalized after 3.5 months of therapy. Muscle biopsy demonstrated only a few fibers with a slightly increased subsarcolemmal SDH activity. Genetic analysis showed homoplasmic 14484/ND6 mutation in all tissues investigated. The clinical phenotype of LHON/14484 in this patient closely resembles that commonly found in European patients. Even if LHON/14484 patients are reported to have a better prognosis for visual recovery, it is possible that the evolution of visual recovery in this patient could have been influenced by therapy as suggested by changes in serum lactate levels. Bioenergetic impairment of skeletal muscle was documented by lactate levels and muscle morphology. The 14484/ND6 mutation behaves as a primary mutation regardless of mtDNA population-specific backgrounds.
我们报告了一名来自北非、携带线粒体DNA 14484/ND6突变的Leber遗传性视神经病变（LHON）患者的临床和遗传学研究。在一年多的时间里，我们跟踪了这位24岁患有LHON的男性患者的眼科病程，其接受艾地苯醌和维生素B12治疗。在治疗前、治疗期间和治疗后评估运动后血清乳酸水平。获取肌肉活检样本进行形态学研究。研究了不同组织中14484/ND6突变的纯合/杂合状态。记录了发病后6个月和确立治疗后3个月视力的恢复情况。基线血清乳酸水平升高，但治疗3.5个月后恢复正常。肌肉活检显示只有少数肌纤维的肌膜下琥珀酸脱氢酶（SDH）活性略有增加。基因分析显示，在所有检测的组织中均存在14484/ND6突变的纯合状态。该患者LHON/14484的临床表型与欧洲患者中常见的表型极为相似。即使据报道LHON/14484患者的视力恢复预后较好，但正如血清乳酸水平变化所提示的，该患者视力恢复的进程可能受到了治疗的影响。通过乳酸水平和肌肉形态学证实了骨骼肌的生物能量损伤。无论线粒体DNA群体特异性背景如何，14484/ND6突变都表现为原发性突变。
