Ramelli Gian Paolo, Gallati Sabina, Weis Joachim, Krähenbühl Stephan, Burgunder Jean-Marc
Department of Pediatrics, Ospedale San Giovanni, Bellinzona, Switzerland.
J Child Neurol. 2006 Mar;21(3):253-5. doi: 10.2310/7010.2006.00047.
We report on a family with a 12-year-old boy who suffered from a maternally inherited syndrome characterized by a combination of sensorineural hearing loss, myoclonus epilepsy, ataxia, severe psychomotor retardation, short stature, and diabetes mellitus. First, he showed a muscular hypotonia with hearing loss; later, he developed a myoclonus epilepsy, growth failure, and severe psychomotor retardation. At the age of 10 years, he developed diabetes mellitus. After initiation of combined ubiquinone and vitamin C treatment, we observed a progression in psychomotor development. Lactate and pyruvate levels in blood and cerebrospinal fluid were normal. No ragged red fibers or ultrastructural abnormalities were seen in a skeletal muscle biopsy. Biochemical assays of respiratory chain complex activities revealed decreased activity of complexes I and IV. By sequence analysis of mitochondrial DNA encoding transfer ribonucleic acids (RNAs), a homoplasmic T to C substitution at nucleotide position 7512 was found affecting a highly conserved base pair in the tRNA(ser(UCN)) acceptor stem. Asymptomatic family members of the maternal line were heteroplasmic for the mutation in blood samples. Analysis of mitochondrial DNA in patients with hearing loss and myoclonus epilepsy is recommended, even in the absence of laboratory findings. Therapeutically, ubiquinone and antioxidants can be beneficial.
我们报告了一个家庭,该家庭中有一名12岁男孩,患有一种母系遗传综合征,其特征为感音神经性听力损失、肌阵挛性癫痫、共济失调、严重精神运动发育迟缓、身材矮小和糖尿病。起初,他表现出肌张力减退伴听力损失;后来,他发展为肌阵挛性癫痫、生长发育不良和严重精神运动发育迟缓。10岁时,他患上了糖尿病。在开始联合使用泛醌和维生素C治疗后,我们观察到其精神运动发育有进展。血液和脑脊液中的乳酸和丙酮酸水平正常。骨骼肌活检未发现破碎红纤维或超微结构异常。呼吸链复合物活性的生化分析显示复合物I和IV的活性降低。通过对编码转移核糖核酸(tRNA)的线粒体DNA进行序列分析,发现在核苷酸位置7512处有一个同质性的T到C替换,影响了tRNA(ser(UCN))受体茎中的一个高度保守碱基对。母系的无症状家庭成员在血液样本中该突变呈异质性。即使没有实验室检查结果,也建议对听力损失和肌阵挛性癫痫患者进行线粒体DNA分析。在治疗上,泛醌和抗氧化剂可能有益。