Long‐term outcome of methylmalonic aciduria after kidney, liver, or combined liver‐kidney transplantation: The French experience

Abstract

Organ transplantation is discussed in methylmalonic aciduria (MMA) for renal failure, and poor quality of life and neurological outcome. We retrospectively evaluated 23 French MMA patients after kidney (KT), liver‐kidney (LKT), and liver transplantation (LT). Two patients died, one after LKT, one of hepatoblastoma after KT. One graft was lost early after KT. Of 18 evaluable patients, 12 previously on dialysis, 8 underwent KT (mean 12.5 years), 8 LKT (mean 7 years), and 2 LT (7 and 2.5 years). At a median follow‐up of 7.3 (KT), 2.3 (LKT), and 1.0 years (LT), no metabolic decompensation occurred except in 1 KT. Plasma and urine MMA levels dramatically decreased, more after LKT. Protein intake was increased more significantly after LKT than KT. Enteral nutrition was stopped in 7/8 LKT, 1/8 KT. Early complications were frequent after LKT. Neurological disorders occurred in four LKT, reversible in one. Five years after KT, four patients had renal failure. The metabolic outcomes were much better after LKT than KT. LKT in MMA is difficult but improves the quality of life. KT will be rarely indicated. We need more long‐term data to indicate early LT, in the hope to delay renal failure and prevent neurodevelopmental complications.

Liver and/or kidney transplantation in amino and organic acid‐related inborn errors of metabolism: An overview on European data

“…While this is a representative number of centers, it might be that nonresponders differed from responders. Thirdly, we did not focus on the reduction of metabolic decompensations after transplantation (if any), since this has already been described in previous studies 6,33‐36 . Lastly, in this study we did not investigate in detail the various postoperative complications, but decided to focus on neurological complications, considering the large effect of neurological complications on mortality, IQ, QOL, and costs.…”

“…Thirdly, we did not focus on the reduction of metabolic decompensations after transplantation (if any), since this has already been described in previous studies. 6,[33][34][35][36] Lastly, in this study we did not investigate in detail the various postoperative complications, but decided to focus on neurological complications, considering the large effect of neurological complications on mortality, IQ, QOL, and costs. It could well be that organ transplantation prevents further decline of cognitive impairment and thereby organ transplantation can be beneficial.…”

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision

“…It is not possible to make evidence‐based statements on improvement of survival with liver transplantation, as the published studies focus on the survival shortly after transplantation, but long‐term comparisons to non‐transplanted patients are absent. This applies to liver, kidney and liver‐kidney transplantations, where overall survival after surgery is around 85% 42‐44 Recommendation If the diagnosis of MMA or PA is suspected, we suggest immediate specific treatment to improve survival in MMA and PA.…”

“…Several (including severe) new neurological sequelae occurred after liver, liver‐kidney and kidney transplantation in MMA and liver transplantation in PA in up to 25% of patients. These included onset of seizures, metabolic stroke, 42,113 Leigh syndrome, 44 worsening of vision and focal leukoencephalopathy, 125 generalised motor neuropathy 85 and general neurological deterioration 116 in MMA patients; and metabolic stroke, 86,104 epilepsy 86 and temporal mesial sclerosis 126 in PA patients.…”

“…This applies to liver, kidney and liver-kidney transplantations, where overall survival after surgery is around 85%. [42][43][44] Recommendation #5. If the diagnosis of MMA or PA is suspected, we suggest immediate specific treatment to improve survival in MMA and PA.…”