Pre‐school neurocognitive and functional outcomes after liver transplant in children with early onset urea cycle disorders, maple syrup urine disease, and propionic acidemia: An inception cohort matched‐comparison study

Abstract

Background Urea cycle disorders (UCD) and organic acid disorders classically present in the neonatal period. In those who survive, developmental delay is common with continued risk of regression. Liver transplantation improves the biochemical abnormality and patient survival is good. We report the neurocognitive and functional outcomes post‐transplant for nine UCD, three maple syrup urine disease, and one propionic acidemia patient. Methods Thirteen inborn errors of metabolism (IEM) patients were individually one‐to‐two matched to 26 non‐IEM patients. All patients received liver transplant. Wilcoxon rank sum test was used to compare full‐scale intelligence‐quotient (FSIQ) and Adaptive Behavior Assessment System‐II General Adaptive Composite (GAC) at age 4.5 years. Dichotomous outcomes were reported as percentages. Results FSIQ and GAC median [IQR] was 75 [54, 82.5] and 62.0 [47.5, 83] in IEM compared with 94.5 [79.8, 103.5] and 88.0 [74.3, 97.5] in matched patients (P‐value <.001), respectively. Of IEM patients, 6 (46%) had intellectual disability (FSIQ and GAC <70), 5 (39%) had autism spectrum disorder, and 1/13 (8%) had cerebral palsy, compared to 1/26 (4%), 0, 0, and 0% of matched patients, respectively. In the subgroup of nine with UCDs, FSIQ (64[54, 79]), and GAC (56[45, 75]) were lower than matched patients (100.5 [98.5, 101] and 95 [86.5, 99.5]), P = .005 and .003, respectively. Conclusion This study evaluated FSIQ and GAC at age 4.5 years through a case‐comparison between IEM and matched non‐IEM patients post‐liver transplantation. The neurocognitive and functional outcomes remained poor in IEM patients, particularly in UCD. This information should be included when counselling parents regarding post‐transplant outcome.

Role of liver transplantation in urea cycle disorders: Report from a nationwide study in Japan

“…Also from other centers, data about the effectiveness of LT in patients with UCDs were reported. [19][20][21][22][23][24] We performed a nation-wide study to investigate the effect of LT in patients with UCDs. Herein, we present the current status of LT in UCDs in our country, and discuss the role of LT on long-term neurodevelopmental outcomes.…”

“…In the recent years, LT for patients with UCDs was performed with increasing frequency in Japan. Also from other centers, data about the effectiveness of LT in patients with UCDs were reported 19‐24 . We performed a nation‐wide study to investigate the effect of LT in patients with UCDs.…”

Motor outcomes in young children pre‐and one‐year post‐liver transplant

“…Research ethics approval was obtained from The Hospital for Sick Children for a single center, retrospective chart review including motor measures and demographic and medical variables of children <6 years of age who underwent an isolated LT between January 2013 and March 2018. Exclusion criteria included children who did not undergo a 1‐year post‐LT assessment and children with metabolic diseases which have a higher risk of neurological injury with an established increased incidence of motor and cognitive delay 15 . Primary chart review was completed by one investigator and verified by the senior investigator.…”

“…Exclusion criteria included children who did not undergo a 1-year post-LT assessment and children with metabolic diseases which have a higher risk of neurological injury with an established increased incidence of motor and cognitive delay. 15 Primary chart review was completed by one investigator and verified by the senior investigator.…”

Physical function in children and adolescents pre‐ and 1‐year post‐liver transplant

“…To create a more homogenous sample, children with a metabolic disease diagnosis and those undergoing a multivisceral transplant (MVT) were excluded due to the increased incidence of motor and cognitive delay in these children. 16,17 Additionally, children were excluded if they did not have a documented 1-year post-LT assessment. Research ethics approval was obtained from SickKids.…”