Background: Since replacing the enzyme-deficient liver with a metabolically normal liver could help regain partial PCC activity, liver transplantation (LT) has emerged as a novel therapeutic option for selected patients with propionic acidemia (PA) who, despite strict dietary and medical intervention, still experience frequent metabolic decompensations or cardiomyopathy. However, current world experience regarding living donor liver transplantation (LDLT) in the treatment of PA patients is limited, especially in terms of using obligate heterozygous carriers as donors. This study aimed to evaluate the clinical outcomes of LDLT in children with PA.
Methods: Patients with PA who underwent LT at our hospital between November 2017 and January 2020 were identified from the liver transplant recipient database. We retrospectively collected demographic data, transplantation details and laboratory measures. The neurodevelopmental delay was assessed using the developmental quotient (DQ). The hepatic expressions of PCCA and PCCB were assessed at the protein level by western blotting.
Results: From November 2017 to January 2020, 7 of the 192 children who underwent LDLT at our institution had been diagnosed with PA (median age, 2.1 years; range, 1.1–5.8 years). The primary indication for transplantation was frequent metabolic decompensations in 6 patients and preventative treatment in 1 patient. Of the seven parental living donors, six were genetically proven obligate heterozygous carriers. During a median follow-up of 23.9 months (range, 13.9–40.2 months), all patients were alive with 100% allograft survival, and no severe transplant-related complications occurred. Cytomegalovirus viremia and Epstein-Barr virus viremia were the most frequent infectious complications, which occurred in 5 and 4 patients, respectively. They all were treated with intravenous or oral ganciclovir. In the case of liberalized protein intake, they did not suffer metabolic decompensation or disease-related complications and made progress in neurodevelopmental delay and body growth, as well as plasma and urinary metabolite levels. In one patient with pre-existing mild dilated cardiomyopathy, her echocardiogram results completely normalized 13.8 months post-transplant. All living donors recovered well after surgery, with no metabolic decompensations or procedure-related complications. Western blotting revealed that the hepatic expressions of PCCA and PCCB in one of the heterozygous donors were comparable to those of the normal healthy control at the protein level.
Conclusions: Our study provides evidence that the hepatic expressions of PCCA and PCCB from the heterozygous donor are comparable to those of the healthy control at the protein level. LDLT using partial liver grafts from asymptomatic obligate heterozygous carrier donors is a viable therapeutic option for selected patients with PA, with no negative impact on both donors' and recipients' postoperative courses.