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.

Figure 1

>A, Pooled plasma leucine values in control subjects (gray circles) and patients with MSUD before (black circles) and 1–11 months and ≥1 year after liver transplantation (open circles). Shaded area represents mean ± 2 SD leucine values in 51 normal children. A single exceptional value of 2170 µM (not shown) was seen in a child who developed severe dehydration at 55 months posttransplantation. B, Plasma molar ratios of leucine to isoleucine (upper panel) and leucine to valine (lower panel) showing intact regulation of BCKDH activity after transplant (open circles). Shaded areas represent mean ± 2 SD molar ratios in normal children.

Figure 2

In 33 pretransplantation patients, there was a strong correlation between IQ (x-axis) and adaptive function (y-axis). Only 3 patients had IQ scores at or above the mean (100; dotted line). One-third had IQ scores in the deficient range (≤70). Shaded areas represent the mean ±2 SD in normal subjects. Gray circles represent Old Order Mennonite subjects and indicate that different cultural background did not bias toward lower test scores. Open circles indicate non-Old Order Mennonite patients.

Figure 3

There was no correlation between age at transplantation and IQ (upper panel) or adaptive scores (lower panel). No correlations were found between test scores and age at diagnosis, number of hospitalizations, number of metabolic crises, or age at transplantation.

Figure 4

A, Change in test scores for a subgroup of 14 patients. Pretransplantation IQ (78 ± 14) and adaptive (81 ± 20) scores were no different at 1 year after transplantation (posttransplantation IQ, 83 ± 15; adaptive, 82 ± 22). Gray shaded areas show the normal mean (dotted line) ± 2 SD. B, Mean percentage change (dotted line) and 95% CI (gray shaded area). IQ increased by an average of 6.2% (95% CI, −1.0% to 12.6%; range, −13% to 30%) at 1 year after transplantation, but the difference was not statistically significant (P = .059).