title: Lipoyltransferase 1 Gene Defect Resulting in Fatal Lactic Acidosis in Two Siblings.
abstract: A term male neonate developed severe intractable lactic acidosis on day of life 1 and died the same day at our institution. The family previously lost another term, female newborn on day of life 1 from suspected sepsis at an outside hospital. After performing an autopsy on the neonate who died at our institution, extensive and lengthy neonatal and parental genetic testing, as well as biochemical analyses, and whole exome sequencing analysis identified compound heterozygous mutations in the lipoyltransferase 1 (LIPT1) gene responsible for the lipoylation of the 2-keto dehydrogenase complexes in the proband. These mutations were also identified in the deceased sibling. The clinical manifestations of these two siblings are consistent with those recently described in two unrelated families with lactic acidosis due to LIPT1 mutations, an underrecognized and underreported cause of neonatal death. Conclusions. Our observations contribute to the delineation of a new autosomal recessive metabolic disorder, leading to neonatal death. Our case report also highlights the importance of an interdisciplinary team in solving challenging cases.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Véronique
authors.initials: V
authors.lastname: Taché
authors.affiliation: Department of Pediatrics, Division of Genomic Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Liga
authors.initials: L
authors.lastname: Bivina
authors.affiliation: Department of Pediatrics, Division of Neonatology, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: White
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gregg
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Deignan
authors.affiliation: Department of Pediatrics, Division of Genomic Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjievd
authors.affiliation: Department of Pediatrics, Division of Neonatology, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Francis R
authors.initials: FR
authors.lastname: Poulain