Neuropaediatric Unit, Necker Hospital, AP-HP, Paris, France.
Dev Med Child Neurol. 2010 Feb;52(2):e1-9. doi: 10.1111/j.1469-8749.2009.03541.x. Epub 2009 Dec 1.
To describe the phenotype and genotype of pyruvate dehydrogenase complex (PDHc) deficiency.
Twenty-two participants with enzymologically and genetically confirmed PDHc deficiency were analysed for clinical and imaging features over a 15-year period.
Four groups were identified: (1) those with neonatal encephalopathy with lactic acidosis (one male, four females; diagnosis at birth); (2) those with non-progressive infantile encephalopathy (three males, three females; age at diagnosis 2-9mo); (3) those with Leigh syndrome (eight males; age at diagnosis 1-13mo); and (4) those with relapsing ataxia (three males; 18-30mo). Seventeen mutations involved PDHA1 (a hotspot was identified in exons 6, 7, and 8 in seven males with Leigh syndrome or recurrent ataxia). Mutations in the PDHX gene (five cases) were correlated with non-progressive encephalopathy and long-term survival in four cases.
Two types of neurological involvement were identified. Abnormal prenatal brain development resulted in severe non-progressive encephalopathy with callosal agenesis, gyration anomalies, microcephaly with intrauterine growth retardation, or dysmorphia in both males and females (12 cases). Acute energy failure in infant life produced basal ganglia lesions with paroxysmal dystonia, neuropathic ataxia due to axonal transport dysfunction, or epilepsy only in males (11 cases). The ketogenic diet improved only paroxysmal dysfunction, providing an additional argument in favour of paroxysmal energy failure.
描述丙酮酸脱氢酶复合物（PDHc）缺陷的表型和基因型。
对 15 年来通过酶学和遗传学确诊为 PDHc 缺陷的 22 名参与者进行临床和影像学特征分析。
确定了四个组：（1）伴有乳酸酸中毒的新生儿脑病（1 名男性，4 名女性；出生时诊断）；（2）进行性婴儿脑病（3 名男性，3 名女性；诊断年龄 2-9mo）；（3） Leigh 综合征（8 名男性；诊断年龄 1-13mo）；和（4）复发性共济失调（3 名男性；18-30mo）。17 种突变涉及 PDHA1（在 Leigh 综合征或复发性共济失调的 7 名男性中，在 6、7 和 8 号外显子中发现了一个热点）。PDHX 基因突变（5 例）与非进行性脑病和 4 例长期存活相关。
确定了两种类型的神经受累。异常的产前脑发育导致严重的非进行性脑病，伴有胼胝体发育不全、脑回异常、小头畸形伴宫内生长迟缓或男性和女性的畸形（12 例）。婴儿期急性能量衰竭导致基底节病变，伴有阵发性肌张力障碍、轴突运输功能障碍引起的神经病性共济失调或仅癫痫（11 例）。生酮饮食仅改善阵发性功能障碍，这为阵发性能量衰竭提供了额外的论据。
