Phenotypic and Neuropathological Characterization of Fetal Pyruvate Dehydrogenase Deficiency
Phenotypic and Neuropathological Characterization of Fetal Pyruvate Dehydrogenase Deficiency
复制标题
DOI：
10.1093/jnen/nlv022
复制
发表时间：
2016-03-01
影响因子：
3.2
通讯作者：
Laquerriere, Annie
中科院分区：
文献类型：
--
作者：
Pirot, Nathalie;Crahes, Marie;Laquerriere, Annie
为了区分丙酮酸脱氢酶缺乏症（PDH）从其他产前神经代谢疾病，从而提高产前诊断，我们描述了影像学检查结果，临床表型，并从3个家庭的胎儿脑病变的分子特征，这种情况。对来自3个无关家系的4例尸检病例进行神经病理学分析，随后进行生化和分子生物学证实PDH复合物缺乏症。在2个家庭中有突变的PDHA 1基因;在第三个家庭中有突变的PDHB基因。所有胎仔均表现出不同严重程度的特征性颅面畸形，无内脏病变，以及相关的脑膨出和发育性幕上和幕下病变。神经发育异常包括小头畸形、迁移异常（厚脑回、多小脑回、室周结节性异位）以及小脑和脑干发育不全伴齿状核和锥体束发育不全。相关的碎屑性病变包括不对称性白质软化、反应性神经胶质增生、大的假性生殖细胞溶解囊肿和基底节钙化。PDH缺乏症的诊断应怀疑产前存在的碎屑和神经发育的损害和一个相对特征性颅面畸形。尸检对于排除其他密切相关的实体至关重要，从而允许进行生物化学和分子确认。
To distinguish pyruvate dehydrogenase deficiency (PDH) from other antenatal neurometabolic disorders thereby improving prenatal diagnosis, we describe imaging findings, clinical phenotype, and brain lesions in fetuses from 3 families with molecular characterization of this condition. Neuropathological analysis was performed in 4 autopsy cases from 3 unrelated families with subsequent biochemical and molecular confirmation of PDH complex deficiency. In 2 families there were mutations in the PDHA1 gene; in the third family there was a mutation in the PDHB gene. All fetuses displayed characteristic craniofacial dysmorphism of varying severity, absence of visceral lesions, and associated encephaloclastic and developmental supra-and infratentorial lesions. Neurodevelopmental abnormalities included microcephaly, migration abnormalities (pachygyria, polymicrogyria, periventricular nodular heterotopias), and cerebellar and brainstem hypoplasia with hypoplastic dentate nuclei and pyramidal tracts. Associated clastic lesions included asymmetric leukomalacia, reactive gliosis, large pseudocysts of germinolysis, and basal ganglia calcifications. The diagnosis of PDH deficiency should be suspected antenatally with the presence of clastic and neurodevelopmental lesions and a relatively characteristic craniofacial dysmorphism. Postmortem examination is essential for excluding other closely related entities, thereby allowing for biochemical and molecular confirmation.