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LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency
Author(s) -
Stowe Robert C.,
Sun Qin,
Elsea Sarah H.,
Scaglia Fernando
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38654
Subject(s) - lactic acidosis , exome sequencing , status epilepticus , pyruvate dehydrogenase complex , hyperglycinemia , encephalopathy , leigh disease , glycine cleavage system , medicine , compound heterozygosity , mitochondrial disease , biology , epilepsy , genetics , phenotype , biochemistry , mutation , glycine , enzyme , gene , mitochondrial dna , amino acid , psychiatry
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.