Acute Metabolic Crises in Maple Syrup Urine Disease After Liver Transplantation from a Related Heterozygous Living Donor

Abstract

Maple syrup urine disease (MSUD) is an autosomal recessive disorder associated with impaired metabolism of branched-chain amino acids (BCAA) leucine, isoleucine, and valine. Children with MSUD suffer from bouts of metabolic decompensation, which may lead to neurological damage. Liver transplantation from unrelated deceased donors has been considered curative. The natural history of the disease following transplantation using a haploidentical (obligate heterozygous) living donor is still unclear, although previously described as favorable. We describe acute metabolic crises in a 20-month-old child with MSUD type II. The first well-documented one occurred 5 months after a successful liver transplantation from his mother. The patient developed encephalopathy with progressive lethargy and seizures after an episode of gastroenteritis with dehydration. Plasma levels of leucine, isoleucine, and valine were markedly elevated and alloisoleucine was detected. He promptly responded to dialysis and BCAA-free dietetic management and subsequently could resume a normal diet. Since then he has had another symptomatic metabolic crisis with seizures. This case strongly suggests that some recipients of liver transplantation from a haploidentical parent possess limited capacity to oxidize BCAA at the time of catabolic stress and dehydration and remain at risk of severe metabolic crises. Thus, careful metabolic monitoring and prompt treatment post liver transplantation are still required to avoid neurological sequelae of MSUD, particularly if the donor is heterozygous for MSUD. Abbreviations BCAABranched-chain amino acids BCKDH Branched-chain keto acid dehydrogenase complex MSUD Maple syrup urine disease

Liver transplantation for neonatal‐onset citrullinemia

“…Following the surgery, both donor and recipient appear not to have clinical consequences from the underlying metabolic defect. More recently, however, there are reports of metabolic decompensation in recipients of heterozygote donors in maple syrup urine disease despite confirmation of normal enzyme activity in the donor in 1 case . ASS activity can be measured indirectly with C 14 ‐citrulline incorporation studies in the cultured skin fibroblasts, but this is time‐consuming and not widely available.…”

Natural history of children and adults with maple syrup urine disease in the NBS-MSUD Connect registry

“…Indeed, BCAA levels in MSUD liver transplant recipients remain approximately two-fold greater than normal [9] , and transient leucine elevations following an illness have been reported [9] . Recently, there have been reports of living donor liver transplants from parents (who are carriers of MSUD) to their affected children [16] , [17] , [18] , [19] , [20] , [21] . Although these patients may also return to a normal diet, they may still have a risk of metabolic decompensation during illness [21] .…”

“…Recently, there have been reports of living donor liver transplants from parents (who are carriers of MSUD) to their affected children [16] , [17] , [18] , [19] , [20] , [21] . Although these patients may also return to a normal diet, they may still have a risk of metabolic decompensation during illness [21] . More data are needed on the long-term outcomes of MSUD patients who receive a living donor liver transplant from a carrier relative.…”

A case of classical maple syrup urine disease that was successfully managed by living donor liver transplantation

“…After LDLT, leucine levels generally stayed stable without intravenous glucose infusion, and even when they did rise, they normalized much faster. Because acute metabolic crisis after LDLT was reported recently, metabolic decompensation may still occur even after LDLT. However, findings from our case suggest that leucine levels would be much easier to control.…”