Renal transplant in methylmalonic acidemia: could it be the best option?

Abstract

Methylmalonic acidemia (MMA) is an inborn error of organic acid metabolism. Patients with severe disease develop many complications despite treatment; often, the disease progresses to severe damage of the central nervous system or to end-stage renal disease (ESRD). When medical treatment is ineffective, liver, kidney, or combined liver and kidney transplantation is advocated. At present, there are no definite guidelines as for the organ to be transplanted, and results are inconsistent. We report on a 27-year-old woman with MMA MUT0. The clinical symptoms developed at age 4 months. She progressed to ESRD and received a kidney transplant in November 1996 at age 17 years. One hundred and twenty months after transplant, renal function is normal; although urinary levels of methylmalonic acid are above normal limits, no episodes of metabolic decompensation have been observed after transplantation. Although liver is the major site of methylmalonyl-CoA mutase activity, this case and similar ones in the literature suggest that the smaller mutase activity present in the transplanted kidney may be sufficient to ensure partial correction of the metabolism of organic acids sufficient to prevent the onset of episodes of metabolic decompensation. It is worth investigating whether kidney transplant can be a safer and more satisfactory alternative to liver transplantation in cases of MMA unresponsive to medical treatment although urine MMA excretion remains significantly elevated.

Combined liver and kidney transplantation in children

“…Common post-operative sequelae included infection, acute rejection, CNI toxicity, and continued neurologic deterioration. Since this report appeared, only a few cases of MMA with isolated living donor LT or isolated KT have been reported [39,40].…”

“…It has been proposed that in this clinical context isolated KT might be a safer alternative to CLKT. The transplanted kidney may be sufficient to ensure the partial correction of metabolism and prevent the onset of episodes of metabolic compensation in some patients [40,42]. At our center, a 10-year old girl with MMA received CLKT 2 years ago; suffered from severe pancreatitis soon after the operation but is now doing clinically well.…”

Correction of Methylmalonic AciduriaIn VivoUsing a Codon-Optimized Lentiviral Vector

“…Liver has been the main target for gene therapy in ameliorating the MMAuria disease, based on the success in liver transplantation (Meyburg and Hoffmann, 2005). However, kidney transplantation alone in a 26-year-old patient resulted in the stabilization of the patient's metabolic decompensation, raising the possibility of considering kidney as a substitute organ for the treatment of MMAuria (Lubrano et al, 2007). This is also suggested by Kaplan et al (2006) and Kasahara et al (2006), who both challenge the rationale of liver transplantation.…”

“…transplantation, but do not show normalization of urinary MMA levels (Lubrano et al, 2007). The role of the kidneys in the whole-body MCM activity is not known, although kidney contains only about 18% of the enzyme activity found in the liver (Andrews et al, 1993;Lubrano et al, 2007).…”

“…The role of the kidneys in the whole-body MCM activity is not known, although kidney contains only about 18% of the enzyme activity found in the liver (Andrews et al, 1993;Lubrano et al, 2007). Liver has been the main target for gene therapy in ameliorating the MMAuria disease, based on the success in liver transplantation (Meyburg and Hoffmann, 2005).…”