Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes
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- 作者：Alessandra Torraco ; Anna Ardissone ; Federica Invernizzi…
- 关键词：MMDS ; IBA57 ; Mitochondrial disorders ; Leukodystrophy
- 刊名：Journal of Neurology
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：264
- 期：1
- 页码：102-111
- 全文大小：
- 刊物类别：Medicine
- 刊物主题：Neurology; Neurosciences; Neuroradiology;
- 出版者：Springer Berlin Heidelberg
- ISSN：1432-1459
- 卷排序：264
文摘
Defects of the Fe/S cluster biosynthesis represent a subgroup of diseases affecting the mitochondrial energy metabolism. In the last years, mutations in four genes (NFU1, BOLA3, ISCA2 and IBA57) have been related to a new group of multiple mitochondrial dysfunction syndromes characterized by lactic acidosis, hyperglycinemia, multiple defects of the respiratory chain complexes, and impairment of four lipoic acid-dependent enzymes: α-ketoglutarate dehydrogenase complex, pyruvic dehydrogenase, branched-chain α-keto acid dehydrogenase complex and the H protein of the glycine cleavage system. Few patients have been reported with mutations in IBA57 and with variable clinical phenotype. Herein, we describe four unrelated patients carrying novel mutations in IBA57. All patients presented with combined or isolated defect of complex I and II. Clinical features varied widely, ranging from fatal infantile onset of the disease to acute and severe psychomotor regression after the first year of life. Brain MRI was characterized by cavitating leukodystrophy. The identified mutations were never reported previously and all had a dramatic effect on IBA57 stability. Our study contributes to expand the array of the genotypic variation of IBA57 and delineates the leukodystrophic pattern of IBA57 deficient patients.