Developmental Outcomes With Early Orthotopic Liver Transplantation for Infants With Neonatal-Onset Urea Cycle Defects and a Female Patient With Late-Onset Ornithine Transcarbamylase Deficiency

Abstract

ABSTRACT. Urea cycle defects (UCDs) typically present with hyperammonemia, the duration and peak levels of which are directly related to the neurologic outcome. Liver transplantation can cure the underlying defect for some conditions, but the preexisting neurologic status is a major factor in the final outcome. Multicenter data indicate that most of the children who receive transplants remain significantly neurologically impaired. We wanted to determine whether aggressive metabolic management of ammonia levels after early referral/transfer to a metabolism center and early liver transplantation would result in better neurologic outcomes. We report on 5 children with UCDs, ie, 2 male patients with X-linked ornithine transcarbamylase deficiency and 2 male patients with carbamoyl phosphate synthase deficiency, all of whom had neonatal presentations and underwent orthotopic liver transplantation before 1 year of age, and 1 female patient with partial X-linked ornithine transcarbamylase deficiency that was intractable to medical therapy, who underwent transplantation at 35 months of age. Developmental testing with the Griffiths scale was performed on 3 occasions each, 12 months apart, up to 45 months after transplantation. Full-scale indices for 3 children who underwent early transplantation showed average developmental quotients of 67. All 5 children had metabolic cures. There were no deaths (30-month survival rate: 100%). One child is currently listed for repeat transplantation because of bile duct stenosis and cirrhosis. We conclude that early liver transplantation and aggressive metabolic management improve early neurologic outcomes for children with UCDs, but longer follow-up monitoring is needed.

Carbamoyl Phosphate Synthetase 1 deficiency in Italy: Clinical and genetic findings in a heterogeneous cohort

“…Our data, consistent with the positive effect of liver transplantation so far reported (Ishida et al, 2009;McBride et al, 2004), make this procedure a therapeutic choice of alternative of the life-long medical treatment.…”

“…It has been reported that early liver transplantation prevents hyperammonemic events and leads to a complete metabolic correction, but pre-existing neurological damage is not reversed (Ishida et al, 2009;McBride et al, 2004). Living-donor transplantation and liver cell and stem cell transplantation are approaches currently discussed and under investigation for the treatment of metabolic disorders (Kasahara et al, 2010;Meyburg and Hoffmann, 2010).…”

Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland

“…Liver transplantation is a curative therapy for UCDs. Best outcome is achieved if liver transplantation is carried out between age 3–12 months and before irreversible brain damage manifests [1, 20, 21]. Hepatocyte transplantation is an experimental therapy which can be used as a bridging procedure.…”

Hepatocyte Transplantation Followed by Auxiliary Liver Transplantation—a Novel Treatment for Ornithine Transcarbamylase Deficiency

“…Early transplantation improves neurodevelopmental outcomes (8), but is limited by the availability of a suitably sized liver for an infant. Moreover, without the native liver, gene therapy is no longer an option should it become available in the future.…”