Cyclic vomiting syndrome and mitochondrial DNA mutations
Cyclic vomiting syndrome and mitochondrial DNA mutations
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DOI：
10.1016/s0140-6736(05)62477-4
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发表时间：
1997-11-01
期刊：
影响因子：
168.9
通讯作者：
Wong, LJC
中科院分区：
文献类型：
--
作者：
Boles, RG;Chun, N;Wong, LJC
周期性呕吐综合征的特点是多次发作的恶心和呕吐。大多数病例发生在学龄前晚期到学龄阶段，每个孩子发作的持续时间和发作之间的间隔都是固定的。1少数病例归因于内分泌（Addison病）、代谢（尿素循环缺陷、卟啉症）和其他疾病，尽管所有病例中约有一半符合既定的腹部偏头痛标准。许多病例仍未得到解释。1例2岁白人女童有喂养困难、产后生长衰竭和中度发育迟缓史。在活检标本的检查中，红斑性皮疹与紫皮病一致，并考虑诊断为rothmond - thomson和Bloom综合征。8个月大时开始出现多次呕吐，并成为临床表现的主要症状。虽然每个月发生一次，但病毒感染和中耳炎也会加重。呕吐频率在每7天发作的第2天达到4-7次/ h的峰值强度。高峰值强度、发作间无呕吐间隔、正常内窥镜检查、上胃肠道和颅磁共振成像检查与周期性呕吐综合征一致。16个月时癫痫发作，发现乳酸性酸中毒，进行线粒体DNA （mtDNA）分析。通过Southern blot检测血液中存在8.1 kb缺失，其中90%的mtDNA突变，并通过测序定位在核苷酸6718和14834之间。这种缺失包括大约一半的线粒体基因组，被认为使突变的mtDNA完全失去功能。患者的家族史在不同的母系亲属中有显著的智力迟钝、震颤和儿童中风，母亲血液中有20%的mtDNA缺失。据我们所知，在这个家族中发现的缺失以前没有报道过。
Cyclic vomiting syndrome is characterised by multiple episodes of nausea and vomiting. Most cases present in the late preschool to school-age years, and in each child the duration of episodes and the interval between them is stereotyped. 1 Rare cases are attributed to endocrine (Addison disease), metabolic (urea-cycle defects, porphyria), and other disorders, although about half of all cases meet established criteria for abdominal migraine. 2 Many cases remain unexplained. A 2-year-old white girl had a history of feeding difficulty, postnatal growth failure, and moderate developmental delay. An erythematous rash was consistent with poikiloderma on examination of a biopsy specimen and diagnoses of Rothmund-Thomson and Bloom syndromes were considered. Multiple episodes of vomiting started at the age of 8 months and came to dominate the clinical picture. Although episodes occurred monthly, they had also been precipitated by viral infections and otitis media. The frequency of vomiting reached a peak intensity of 4–7 per h on the second day of each 7-day episode. High peak intensity, vomiting-free intervals between episodes, and normal endoscopy, upper gastrointestinal and cranial magnetic resonance imaging studies were consistent with cyclic vomiting syndrome. 2Onset of seizures at age 16 months and finding of lactic acidosis led to analysis of mitochondrial DNA (mtDNA). An 8· 1 kb deletion with 90% mutant mtDNA in blood was determined by Southern blot and localised between nucleotides 6718 and 14834 by sequencing. Comprising about one half of the mitochondrial genome, this deletion is thought to render the mutated mtDNA completely non-functional. The patient’s family history was remarkable for mental retardation, tremor, and childhood stroke in different matrilineal relatives, and the mother’s blood showed 20% deleted mtDNA. The deletion found in this family has not, to our knowledge, been previously reported.