Early Liver Transplantation for Neonatal-Onset Methylmalonic Acidemia

Abstract

With conventional dietary treatment, the clinical course of methylmalonic acidemia due to cobalamin-unresponsive methylmalonyl-CoA mutase (MCM) deficiency is characterized by the persistent risk of recurrent life-threatening decompensation episodes with metabolic acidosis, hyperammonemia, and coma. Liver transplant has been proposed as an alternative treatment and anecdotally attempted in the last 2 decades with inconsistent results. Most criticisms of this approach have been directed at the continuing risk of neurologic and renal damage after transplant. Here, we report the perioperative and postoperative clinical and biochemical outcomes of 2 patients with severe MCM deficiency who underwent early liver transplant. In both cases, liver transplant allowed prevention of decompensation episodes, normalization of dietary protein intake, and a marked improvement of quality of life. No serious complications have been observed at 12 years' and 2 years' follow-up, respectively, except for mild kidney function impairment in the older patient. On the basis of our experience, we strongly suggest that liver transplant should be offered as a therapeutic option for children with cobalamin-unresponsive MCM deficiency at an early stage of the disease.

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

“…Isolated KT was also previously reported, but with a short follow‐up . Protein restriction was moderately eased, and the quality of life improved.…”

“…Isolated KT was also previously reported, but with a short follow-up. 12 Protein restriction was moderately eased, and the quality of life improved. Comparing the long-term data on these patients to ours would be important for future indications.…”

“…[2][3][4][5] Liver transplantation (LT), kidney transplantation (KT), or combined liver and kidney transplantation (LKT) have been proposed for renal failure or as an enzyme replacement therapy for frequent metabolic decompensations, but also to prevent long-term complications. [6][7][8][9][10][11][12][13][14] Several reports emphasized the improved quality of life after LT. 10,15,16 However transplantation is not a cure, and neurological and renal outcomes remain a concern. 11 We wanted to report here our experience with KT, LKT, and LT in MMA patients and the changes overtime in our clinical decision-making, in order to better discuss indications and timing.…”

Toxic‐metabolic Risk Factors in Pediatric Pancreatitis

“…It is understood that other, but extremely rare, metabolic risk factors of pancreatitis include methylmalonic acidemia (7), proprionic acidemia (8), and some urea cycle disorders, such as ornithine carbamoyltransferase deficiency (9) Metabolic syndromes typically present with multisystem involvement and associated symptoms that lead to their consideration. For example, methylmalonic acidemia presents with failure to thrive, vomiting, anemia, thrombocytopenia, hypotonia, renal disease, and developmental delay (10). Propionic acidemia is associated with protein intolerance leading to symptoms of vomiting, lethargy, ketosis, neutropenia, thrombocytopenia, and developmental delay (11).…”

Living donor liver transplantation for inborn errors of metabolism – An underutilized resource in the United States

“…The timing of transplantation has been debated and depends on the type and severity of disease. There have been several reports describing less long‐term neurological damage when children with UCD or MMA are transplanted before the age of one yr as compared to those transplanted at an older age . Obstacles to performing liver transplant at this young age include the availability and size of donor organs as well as the tenuous course of the patients' metabolic disease.…”