Differential Intraoperative Effect of Liver Transplant in Different Inborn Errors of Metabolism.

Liver transplant (LT) is a therapeutic option for a growing number of inborn errors of metabolism (IEM), including some disorders not confined to the liver. Clinical advantages of LT in maple syrup urine disease (MSUD), methylmalonic acidemia (MMA), and argininosuccinic aciduria (ASA) have been reported. However, no information on the early metabolic effect of LT after portal reperfusion is available in these disorders. Here we describe the intraoperative differential metabolic outcome of LT in MSUD, MMA, and ASA. In these IEM, LT promptly cleared toxic metabolites to safe concentrations. In MSUD, leucine concentration reached physiological concentration within 12 hours after portal reperfusion. In MMA and ASA, LT allowed faster clearance of methylmalonate and argininosuccinate, respectively, both dropping by ∼90% within the first hour after portal reperfusion. The early biochemical benefits of LT in MSUD, MMA, and ASA demonstrate its immediate effectiveness in protecting patients from intercurrent metabolic decompensations.

Argininosuccinic Aciduria-A Rare Indication for Liver Transplant: Report of Two Cases.

Argininosuccinic aciduria is a urea cycle disorder caused by an argininosuccinate lyase enzyme deficiency that ends with nitrogen accumulation as ammonia. Argininosuccinic aciduria patients are at risk for long-term complications including poor neurocognitive outcome, hepatic disease, and systemic hypertension despite strict pharmacologic and dietary therapy. As the liver is the principle site of activity of the urea cycle, it is logical that a liver transplant should be an option, with careful patient selection, even in the absence of cirrhosis. We present 2 pediatric argininosuccinic aciduria patients who underwent a living-donor liver transplant from their mothers. After the liver transplant, the general well-being of the patients and their quality of life improved significantly. Liver transplant should be an option for argininosuccinic aciduria patients to prevent further neurologic deterioration and improve the patient's quality of life.

Report of 3 Patients With Urea Cycle Defects Treated With Related Living-Donor Liver Transplant.

Urea cycle defects are a group of metabolic disorders caused by enzymatic disruption of the urea cycle pathway, transforming nitrogen to urea for excretion from the body. Severe cases present in early infancy with life-threatening metabolic decompensation, and these episodes of hyperammonemia can be fatal or result in permanent neurologic damage. Despite the progress in pharmacologic treatment, long-term survival is poor especially for severe cases. Liver transplant is an alternative treatment option, providing sufficient enzymatic activity and decreasing the risk of metabolic decompensation. Three patients with urea cycle defects received related living-donor liver transplants at our hospital. Patients presented with late-onset ornithine transcarbamylase deficiency, argininosuccinate lyase deficiency, and citrullinemia. Maximum pretransplant ammonia levels were between 232 and 400 µmol/L (normal range is 18-72 µmol/L), and maximum posttransplant values were 52 to 94 µmol/L. All patients stopped medical treatment and dietary protein restriction for urea cycle defects after transplant. The patient with late-onset ornithine transcarbamylase deficiency already had motor deficits related to recurrent hyperammonemia attacks pretransplant. A major improvement could not be achieved, and he is wheelchair dependent at the age of 6 years. The other 2 patients had normal motor and mental skills before transplant, which have continued 12 and 14 months after transplant. Hepatic artery thrombosis in the patient with the ornithine transcarbamylase deficiency, intraabdominal infection in the patient with argininosuccinate lyase deficiency, and posterior reversible encephalopathy syndrome in the patient with citrullinemia were early postoperative complications. Histopathologic changes in livers explanted from patients with ornithine transcarbamylase deficiency and citrullinemia were nonspecific. The argininosuccinate lyase-deficient patient had portoportal fibrosis and cirrhotic nodule formation. In conclusion, liver transplant was a lifesaving procedure for our patients. Proper timing for transplant is important because high ammonia levels may result in permanent neurologic damage; however, transplant at younger ages also may increase morbidity.