LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency.
Am J Med Genet A
; 176(5): 1184-1189, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29681092
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spasms, Infantile
/
Acyltransferases
/
Pyruvate Dehydrogenase Complex Deficiency Disease
/
Leigh Disease
/
Genetic Association Studies
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
/
Infant
/
Male
Language:
En
Journal:
Am J Med Genet A
Journal subject:
GENETICA MEDICA
Year:
2018
Document type:
Article