Combined liver–kidney transplant for the management of methylmalonic aciduria: A case report and review of the literature

Abstract

Over 27 cases of liver transplant, kidney transplant and combined liver-kidney transplant have been reported for the treatment of methylmalonic aciduria. We describe a case of a 5-year-old boy who underwent combined liver-kidney transplant (CLKT) for phenotypic mut0 disease. His history was notable for more than 30 hospitalizations for severe acidosis, metabolic strokes, liver disease, pancreatic disease, chronic renal insufficiency with interstitial nephritis, and decreased quality of life. Post-CLKT, there was a marked reduction in serum (80%) and urine MMA levels (90%) as well as a cessation of metabolic decompensations. Neurologic deterioration continued post-CKLT manifested as a cerebellar stroke. The clinical details and therapeutic implications of solid organ transplant for methylmalonic aciduria are discussed.

Combined liver and kidney transplantation in children

“…MMA is a rare disease (1:80,000) and to date the criteria for transplantation are not well-established [37]. A literature survey in 2008 identified 27 MMA patients who had undergone transplantation, including six KT, 15 LT, and six CLKT [38]. All diagnoses were made within the first 4 months of life, and the average age at transplantation was 9.2 years.…”

“…Five deaths occurred post-transplantation-four from infection and one due to metabolic decompensation. All patients with CLKT were alive at the time of the literature survey [38]. Common post-operative sequelae included infection, acute rejection, CNI toxicity, and continued neurologic deterioration.…”

Barriers to Transplantation in Adults with Inborn Errors of Metabolism

“…Transplantation can be done to provide organ replacement therapy as in the case of patients with renal failure from Fabry disease (FD) (Weidemann et al 2010) or methylmalonic aciduria (MMA) (McGuire et al 2008). It can be a life-saving therapy for patients with acute metabolic decompensation from unstable conditions like maple syrup urine disease (Mazariegos et al 2012) and urea cycle defects (UCD) (Morioka et al 2005).…”

Correction of Methylmalonic AciduriaIn VivoUsing a Codon-Optimized Lentiviral Vector

“…Recently, liver and combined liver-kidney transplantations have been attempted with the aim of replacing MCM activity, thus reducing the need for dietary restriction and preventing long-term complications (Mc Guire et al, 2008).…”

“…To date, 27 cases of organ transplantation have been published, these being liver transplantation (15 out of 27), kidney transplantation (6 out of 27), and combined liverkidney transplantation (6 out of 27) (Mc Guire et al, 2008). Although this therapeutic option appears to protect the patients against acute metabolic decompensation, and the quality of life is improved, the effectiveness of this treatment is still controversial (Kaplan et al, 2006;Kasahara et al, 2006).…”