Therapeutic potential of living donor liver transplantation from heterozygous carrier donors in children with propionic acidemia

Background Current world experience regarding living donor liver transplantation (LDLT) in the treatment of propionic acidemia (PA) 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 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. Results 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. 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 blood 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 LDLT using partial liver grafts from asymptomatic obligate heterozygous carrier donors is a viable therapeutic option for selected PA patients, with no negative impact on donors' and recipients' clinical courses.

Automated summary

This study evaluates the clinical outcomes of living donor liver transplantation (LDLT) in children with propionic acidemia (PA), using obligate heterozygous carriers as donors. The results show that all patients had a successful transplantation with no severe complications, and the living donors also recovered well with no complications. The study suggests that LDLT using partial liver grafts from asymptomatic obligate heterozygous carriers is a viable treatment option for selected PA patients.