Abstract: FR-PO099

Late Onset Glutaric Acidemia Type 2 Caused by a Novel ETFDH Gene Mutation Presenting with Fulminant Hepatic and Acute Renal Failure

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Wang, Xiangling, University Texas Southwestern Medical Center, Dallas, Texas, United States
  • Tanriover, Bekir, University Texas Southwestern Medical Center, Dallas, Texas, United States
  • Lu, Christopher Y., University Texas Southwestern Medical Center, Dallas, Texas, United States
  • Ghanta, Mythili, University Texas Southwestern Medical Center, Dallas, Texas, United States
Background

Glutaric acidemia type 2 (GA 2) is an autosomal recessive disorder caused by deficiency of electron transfer flavoprotein. A vast majority of cases were diagnosed in early childhood and late onset cases were thought to present with mild clinical symptoms. Here we report one late onset case with novel ETFDH missense mutation presenting with metabolic decompensation requiring liver transplant and hemodialysis.

Methods

A 30-year-old African American female presented with fatigue, nausea, vomitings and abdominal pain. Hospital course was complicated by severe hypoglycemia, acute cardiopulmonary failure requiring mechanical ventilation, acute liver failure with biopsy findings of diffuse micro steatosis, rhabdomyolyis and acute renal failure requiring continuous renal replacement therapy. She emergently received a liver transplant (LT). Pretransplant plasma, concentrations of fatty acids C6-C16 were elevated suggestive of GA 2. Sanger sequencing disclosed homozygous missense mutation in ETFDH gene (c.1019 T>A; p.Phe340Tyr). This mutation has never been reported as pathogenic or benign variant in population database. Silico analysis revealed this novel mutation as likely pathogenic. One month after LT she was transferred to rehab facility with good allograft function tolerating 1-2 hours of moderate physical activity and recovered renal function to remain off dialysis.

Conclusion

Elevated fatty acids along with identification of this novel mutation support the diagnosis of late onset GA 2. In addition, inborn errors of metabolism should be suspected even in adults who present with unexplained rhabdomyolysis and acute renal failure.