Congenital cataract as the first symptom of a neuromuscular disease caused by a novel single large-scale mitochondrial DNA deletion
Congenital cataract as the first symptom of a neuromuscular disease caused by a novel single large-scale mitochondrial DNA deletion
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DOI：
10.1038/sj.ejhg.5200975
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发表时间：
2003-05-01
影响因子：
5.2
通讯作者：
Melegh, B
中科院分区：
文献类型：
--
作者：
Bene, J;Nádasi, E;Melegh, B
这里报道的男性先证者是健康非近亲父母的第二个孩子，足月时具有适当的人体测量参数。他唯一的临床症状是出生时患有双侧先天性白内障并伴有斜视，8个月大时双眼晶状体均被手术摘除。此后的围产期和婴儿期临床上平安无事，精神运动发育几乎正常。 6岁时，他因轻微肌肉无力、轻微上睑下垂、眼球震颤和体力活动减少而住院。不久之后，他的全身状况恶化，出现步态共济失调、吞咽困难和言语困难，随后迅速进展性全身性共济失调，并出现肌病。头颅MRI可检测到典型的进行性灰质变性伴基底节局灶性坏死，这是Leigh型神经病理学的特征，肌肉组织学显示呈参差不齐的红色纤维。 7.5岁时，意外出现左侧偏瘫并伴有类似MELAS综合征的言语障碍，1.5天内康复。患者线粒体DNA显示单个6.7 kb大规模缺失，包含7 817至14 536 bp。该病例首次报告了经证实与先天性白内障相关的 mtDNA 突变，这是后来发展的进行性神经肌肉疾病的第一个临床症状，表现为 Leigh 神经病理学、参差不齐的红纤维组织病理学和中风样发作的组合。
The male proband reported here was born with appropriate anthropometric parameters at term as the second child of healthy nonconsanguineous parents. His only clinical symptom was bilateral congenital cataracts with strabismus at birth, and both lenses were removed surgically at the age of 8 months. The perinatal and infantile period thereafter was clinically uneventful and his psychomotor development appeared almost normal. At the age of 6 years he was hospitalized for slight muscle weakness, minor ptosis, nystagmus and decreased physical activity. Soon after, his general condition worsened, gait ataxia presented, dysphagia and difficulty of speech followed by rapidly progressive generalized ataxia, and myopathy developed. Typical progressive gray matter degeneration with focal necrosis in the basal ganglia characteristic of the Leigh type of neuropathology could be detected by cranial MRI, the muscle histology showed ragged-red fibers. At the age of 7.5 years, unexpected left side hemiparesis with speech disability resembling that seen in MELAS syndrome developed, from which he recovered within 1.5 days. The mtDNA of the patient showed single 6.7 kb large-scale deletion harboring between 7817 and 14 536 bp. This case represents the first report of a verified mtDNA mutation associated with congenital cataracts as the first clinical sign of a later developing progressive neuromuscular disease presented with a combination of Leigh neuropathology, ragged-red fiber histopathology and stroke-like attack.