Researchers at UC Davis have identified a new metabolic disorder that affects newborns and leads to death hours after their birth. Identification of the genetic defect has meant the delivery of a healthy newborn to a mother who earlier had lost two other newborns to the condition.
The three-year investigation of the loss of the younger siblings resulted in the identification of the genetic mutation, which causes lactic acidosis — excessive acid build-up — cardiac arrest and death.
The cases are described online today in Case Reports in Obstetrics and Gynecology.
Identification of the disorder was accomplished by a team of experts and the whole exome sequencing of both of the infants.
“This case really humbled us. It made us all think outside the box in terms of possible etiologies,” said Veronique Tache´, assistant professor of obstetrics and gynecology. “To go through one newborn loss is tragic enough, but two consecutive newborn losses, without an explanation, is unimaginable. I really believe the combined efforts of all of our team, leveraging each person’s unique strength, made all the difference.”
The two earlier deaths occurred two years apart in the same mother. In both instances, the apparently healthy mother had uncomplicated deliveries of seemingly healthy babies. Yet in both instances the newborns’ conditions rapidly deteriorated and subsequently they expired, in the first instance in less than two hours and in the second 12 hours later.
Upon the loss of the second newborn, the care team requested whole exome sequencing of the newborn, which showed abnormalities in the lipoyltransferase 1 (LIPT1) gene which had been recently identified as a cause of metabolic acidosis in infants. Lactic acidosis is the occurrence of lactate accumulation in the body and a pH of less than 7. Severe and prolonged lactic acidosis results in multi-organ energy failure and may prove fatal.
With the finding of the LIPT1 variants, a member of the team, Genetic Counselor Liga Bivina, obtained DNA samples from the first newborn to determine whether that infant was affected as well. The sample was sent to UCLA and tested for the same LIPT1 mutation seen in the second infant. The test confirmed the mutation in the first child.
During the course of the genetic evaluations the mother became pregnant a third time. She underwent chorionic villous sampling, a procedure that can identify chromosomal abnormalities and other inherited disorders associated with birth defects and genetic diseases. The third child was discovered to not have the genetic disorder, and the mother delivered a healthy, full-term child, who is thriving.
“This couple had a strong impact on me personally and on my work taking care of women with high-risk pregnancies,” Tache´ said. “It’s important to not underestimate the power of teamwork, and the desire for a group of people in various specialties and across different universities to put their minds together. It is hard to put into words the joy I felt seeing this wonderful couple take home their first child.”
Other study authors are Liga Bivina, Department of Pediatrics, Division of Genomic Medicine; Sophie White, Department of Pediatrics, Division of Neonatology; Jeffrey Gregg, Department of Pathology and Laboratory Medicine; Simeon A. Boyadjiev, Department of Pediatrics, Division of Genomic Medicine; and Francis Poulain, Department of Pediatrics, Division of Neonatology, all of UC Davis; and Joshua Deignan, Department of Pathology and Laboratory Medicine, UCLA.
Jeffrey Gregg was supported by P30 Core Grant CA93373-01. Simeon Boyadjiev was supported by the Children’s Miracle Network Endowed Chair.