Twenty-Four Years of Liver Transplantation for Inherited Metabolic Disorders: Have We Improved Nutritional Outcomes?

Introduction: Liver transplantation is an established therapeutic option for selected inborn errors of metabolism (IEM), providing metabolic stabilisation and reducing disease-related morbidity. However, the nutritional and growth outcomes of children undergoing transplantation for IEM remain poorly characterised. We retrospectively evaluated 24 years of nutritional and clinical outcomes following liver transplantation in children with propionic acidemia (PA), methylmalonic acidemia (MMA), glycogen storage disease type 1a/b (GSD1a/b), and urea cycle disorders (UCDs). Methods: Clinical and nutritional data were retrospectively extracted from hospital records. Of 58 children with IEM who underwent liver transplantation, 46 survived (79%). Survivors included children with PA/MMA (n = 13; PA, n = 4/10; MMA, n = 0/3), neonatal-(n = 9/10) and late-onset UCDs (n = 7/8), GSD1a/b (n = 9/9), tyrosinemia type I (n = 14/14), and maple syrup urine disease (n = 3/4). Detailed nutritional analyses were conducted in 27 surviving children, excluding those with tyrosinemia (n = 14), maple syrup urine disease (n = 3), and two children with PA. Data included age at diagnosis and transplantation, post-transplant follow-up, hospital admissions, anthropometric measures, nutritional support, energy and protein intake, micronutrient intake, and nutritional biochemistry where available. Pre- and post-transplant nutritional intake was assessed against reference nutrient intake (RNI) and estimated average requirement (EAR). Results: Overall survival was lowest in MMA (0%) and PA (40%) compared with 100% in GSD1a/b, 90% in late-onset UCDs, and 88% in neonatal-onset UCDs. PA and neonatal-onset UCDs were typically diagnosed within the first 5 days of life, whereas median age at diagnosis was 21 months for late-onset UCDs and 3 months for GSD1a/b. Median age at transplantation ranged from 2.2 years in neonatal-onset UCDs to 4.9 years in late-onset UCDs, with a median of 12 years (5–24 years) post-transplant follow-up. Before transplantation, 21/27 children (78%) required gastrostomy or nasogastric tube feeding. Hospital admissions statistically significantly decreased across all diagnostic groups; the incident rate ratio (IRR) was 0.32 for GSD, 0.04 for PA, 0.12 for neonatal and 0.48 for late-onset UCDs. Despite this reduction in disease-related morbidity, growth did not improve. Weight and height z-scores declined or remained unchanged across all diagnostic groups, with significant deterioration in height in children with PA (p < 0.0289) and GSD (p < 0.0002). Before transplantation, median energy intake was 72 kcal/kg/day (96% of EAR) and protein intake was 1.2 g/kg/day (120% of RNI). The median time for discontinuation of tube feeding was 18 months after transplantation, although three children, one each with PA, GSD1b, and late-onset UCD, remained dependent on enteral feeding. Conclusions: In this single-centre retrospective cohort, liver transplantation was associated with reduced hospital admission frequency, but improvements in linear growth were not consistently observed. Interpretation is limited by small diagnostic subgroups, missing post-transplant dietary data, differences in follow-up and changes in clinical practice across the study period. These findings support prospective evaluation of structured nutritional and growth surveillance after transplantation, including multidisciplinary assessment before withdrawal of enteral feeding.