Disclosure(s): No relevant financial relationship(s) to disclose.
First Author: Michael Salomon, MD Co-Author: Avneep Aggarwal, MD, FASA – Doctor, Cleveland Clinic
Introduction: Alpers-Huttenlocher syndrome (AHS) is a rare congenital mitochondrial disease caused by deletions in polymerase gamma (POLG) gene. It typically presents in childhood with seizures and liver failure, but adult-onset cases are exceedingly rare and diagnostically challenging. Liver transplantation has historically been avoided due to concerns over continued neurologic deterioration. We present a critically ill adult with known AHS and acute liver failure managed successfully with orthotopic liver transplantation (OLT) in the ICU.
Description: A 21-year-old woman with genetically confirmed AHS due to biallelic pathogenic POLG variants presented to the ICU with new-onset refractory status epilepticus, persistent hypoglycemia, coagulopathy, and acute liver failure. She required vasopressor support and continuous renal replacement therapy for hepatorenal syndrome. Valproate had been recently initiated, and liver biopsy suggested both drug-induced liver injury and underlying disease progression. Her MELD-Na was 31 on admission. Despite her critical state, she was evaluated and approved by a multidisciplinary transplant team. She underwent deceased donor OLT on ICU day three. Her postoperative course was notable for resolution of hepatic dysfunction and resolution of her status epilepticus, although she continued to experience residual seizures and psychomotor symptoms.
Discussion: AHS in adults is exceptionally rare, with estimates suggesting fewer than one case per two million individuals. This case highlights the complexity of managing acute liver failure in a critically ill patient with underlying AHS. Valproate can unmask or accelerate hepatic failure in POLG-related disease, typically recognized only once critical decompensation has occurred. While OLT has been considered contraindicated in AHS due to ongoing neurologic decline, this case illustrates that in selected patients, transplant during active multiorgan failure may be lifesaving. Although conclusions cannot be drawn from a single case, this report underscores the need for early recognition, multidisciplinary coordination, and individualized decision-making in the ICU when managing rare mitochondrial syndromes.
