Abstract
BackgroundCurrent 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.MethodsFrom 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.ResultsDuring 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.ConclusionsLDLT 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.
Highlights
Propionic acidemia (PA; Online Mendelian Inheritance in Man [OMIM] #606054) is an ultrarare autosomal-recessive disorder of metabolism characterized by biallelic pathogenic variants on chromosome 13q32.3 (PCCA) or 3q22.3 (PCCB), resulting in the deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC) [1]
The diagnosis of propi‐ onic acidemia (PA) was confirmed through a combination of clinical manifestations, typical biochemical findings, and identification of pathogenic variants in PCCAor PCCB on molecular genetic testing (Table 1; Fig. 1)
For the first time, we found that at the protein level, the hepatic expressions of PCCA and PCCB in the heterozygous donor were comparable to the healthy donor
Summary
Propionic acidemia (PA; Online Mendelian Inheritance in Man [OMIM] #606054) is an ultrarare autosomal-recessive disorder of metabolism characterized by biallelic pathogenic variants on chromosome 13q32.3 (PCCA) or 3q22.3 (PCCB), resulting in the deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC) [1]. Zeng et al Orphanet Journal of Rare Diseases (2022) 17:62 propionyl-CoA-related metabolites These circulating toxic metabolites continuously cause damage to various organs and tissues throughout the body [2]. Despite good compliance with long-term conservative management consisting of individualized nutritional intervention, levocarnitine supplementation, and oral metronidazole, the overall prognosis of PA patients remains poor [6]. Patients surviving their initial metabolic decompensation episode may suffer frequent metabolic decompensations and disease-related long-term multiorgan sequelae such as growth impairment, neurocognitive deficits, cardiomyopathy, pancreatitis, or chronic kidney disease [7, 8]. This study aimed to evaluate the clinical outcomes of LDLT in children with PA
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