Liver Transplantation for Classical Maple Syrup Urine Disease: Long-Term Follow-Up in 37 Patients and Comparative United Network for Organ Sharing Experience

Abstract

Objective To assess clinical and neurocognitive function in children who have undergone liver transplantation for classical maple syrup urine disease (MSUD). Study design A total of 35 patients with classical MSUD (age 9.9 ± 7.9 years) underwent liver transplantation between 2004 and 2009. Six patients donated their liver to recipients without MSUD (“domino” transplant). We analyzed clinical outcomes for our cohort and 17 additional cases from the national United Network for Organ Sharing registry; 33 patients completed IQ and adaptive testing before transplantation, and 14 completed testing 1 year later. Results Patient and graft survival were 100% at 4.5 ± 2.2 years of follow-up. Liver function was normal in all patients. Branched-chain amino acid levels were corrected within hours after surgery and remained stable, with leucine tolerance increasing more than 10-fold. All domino transplant recipients were alive and well with normal branched-chain amino acid homeostasis at the time of this report. Patient and graft survival for all 54 patients with MSUD undergoing liver transplantation in the United States during this period were 98%and 96%, respectively. One-third of our patients were mentally impaired (IQ ≤ 70) before transplantation, with no statistically significant change 1 year later. Conclusion Liver transplantation is an effective long-term treatment for classical MSUD and may arrest brain damage, but will not reverse it.

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

“…However, we do not know if the patient described by Mazariegos with an asymptomatic increase in leucine after transplant, received it from a heterozygous carrier or not. The case of our patient reinforces once more the importance of the following recommendations of Mazariegos et al: (1) Clinicians should continue monitoring amino acids in post transplant patients, particularly those who develop serious catabolic illness or unexplained encephalopathy; (2) visceral ischemia, hepatic vascular compromise, dehydration, or factors restricting hepatic blood flow can compromise BCAA clearance by the graft (Mazariegos et al 2012). …”

“…Mazariegos et al suggested that visceral ischemia, hepatic vascular compromise, dehydration or factors restricting hepatic blood flow can compromise BCAA clearance by the graft (Mazariegos et al 2012). It is not likely that any of these played a major role in our patient's metabolic crises because both his liver echo-Doppler and liver function tests were normal at the time of the crisis at 5 months post transplant, which was the most serious one.…”

“…Surprisingly, this patient did not develop obvious neurological symptoms during this episode. His BCAA levels normalized within a few days of intravenous hydration, without specific metabolic treatment (Mazariegos et al 2012).…”

“…Thirty-five patients (age, 9.9 AE 7.9 years) were followed between 2004 and 2009. They showed that liver transplant is an effective long-term treatment for MSUD and may arrest further brain damage (Mazariegos et al 2012). However, they did report a child who developed hyperleucinosis during an episode of gastroenteritis and dehydration; this episode occurred 55 months post transplant from a non-related donor.…”

“…However, the non-symptomatic metabolic crisis described by Mazariegos and the events described in our patient indicate that the capacity of a grafted liver to oxidize BCAA can be overwhelmed by catabolic stress and dehydration and that the protection afforded by the liver transplant may not be complete in some cases. The liver probably accounts for only 9 to 13% of the whole body BCKDH activity enzyme activity; the rest is found in other tissues, mainly in muscle (54-66%) (Mazariegos et al 2012).…”