LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency

作者：Stowe Robert C; Sun Qin; Elsea Sarah H; Scaglia Fernando^*

来源：American Journal of Medical Genetics, Part A, 2018, 176(5): 1184-1189.

DOI：10.1002/ajmg.a.38654

• early infantile epileptic encephalopathy
• global metabolomic profile
• ketogenic diet
• lipoyltransferase 1
• pyruvate dehydrogenase deficiency
• whole exome sequencing

Lipoic acid is an essential cofactor for the mitochondrial 2-ketoacid dehydrogenase complexes and the glycine cleavage system. Lipoyltransferase 1 catalyzes the covalent attachment of lipoate to these enzyme systems. Pathogenic variants in LIPT1 gene have recently been described in four patients from three families, commonly presenting with severe lactic acidosis resulting in neonatal death and/or poor neurocognitive outcomes. We report a 2-month-old male with severe lactic acidosis, refractory status epilepticus, and brain imaging suggestive of Leigh disease. Exome sequencing implicated compound heterozygous LIPT1 pathogenic variants. We describe the fifth case of LIPT1 deficiency, whose phenotype progressed to that of an early infantile epileptic encephalopathy, which is novel compared to previously described patients whom we will review. Due to the significant biochemical and phenotypic overlap that LIPT1 deficiency and mitochondrial energy cofactor disorders have with pyruvate dehydrogenase deficiency and/or nonketotic hyperglycinemia, they are and have been presumptively under-diagnosed without exome sequencing.

• 出版日期2018-5