Table 3.

Reports of IV BCAA-free amino acid formula administration in pediatric MSUD patients.

Author, Year	Patients, episodes	Treatment	Outcomes	Comments
De Lonlay et al. (17)	126 episodes total: pediatric group (oral/enteral 65; IV 14)	Episodes treated with oral/enteral BCAA-free formula or IV BCAA-free solution	Oral/enteral vs. IV): percentage reaching normalization (83.1%, n = 54 vs. 85.7%, n = 12); mean (±SD) time to first leucine normalization (68.3 h [±53.4] vs. 84.1 h [±59.8]); and mean (±SD) time to episode resolution (8.8 days ( ± 6) vs. 6.8 days (±3.6), p = NS). The duration of hospitalization was the same in both treatment groups (mean 6.6 days)	Enteral or oral BCAA-free formula was frequently used in children (94%, adults: 44.4%) and the IV formulation was frequently used in adults (85.2%, children: 21.7%).
Abi-Wardé et al. (25)	20 pediatric patients out of 35 patient total	14 patients (including 6 <6 years) treated with IV BCAA-free solution (including adults)	Patients on oral BCAA spent 4.1 (1.4) days at the hospital, whereas IV BCAA patients spent 3.6 (1.3) days. Leucine level normalization was faster when patients were treated IV rather than orally (p = 0.015)	A clear comparison of IV vs. oral BCAA-free solution was not reported for the pediatric subset; haemodialysis was not excluded.
Alili et al. (19)	30 acute episodes in pediatric patients	IV BCAA free solution	At discharge, 82% (n = 18/22) of children and 84% (n = 67/80) of adults had a normalized leucine concentration	Haemodialysis in 4 children. Parenteral BCAA-free solution appeared effective and safe, providing an alternative to nasogastric route.
Morton et al. (16)	36 neonates, 5 received IV-PN	IV-PN: intravenous dextrose and amino acid mixture devoid of leucine, isoleucine, and valine	- Days until Leucine <400 μmol/L in IV-PN group (range): 3.5–8. - The average length of hospitalization in the series was 6 days (range 4–8 days).	- Asymptomatic at-risk infants were managed exclusively with oral feeding
Yoshino et al. (11)	Of 13 patients, 1 infant (2-year-old) received IV hyperalimentation	IV hyperalimentation	Leucine level reduction from 36.4 to 14.1 μmol/L in 3 days	Patient was also treated with haemodialysis.
Koga et al. (10)	8-year-old	IV hyperalimentation before, during and after surgery	Serum levels of BCAA increased 4.6- to 9.5-fold within 24 h after the operation but with no clinical symptoms of ketoacidotic attack nor any laboratory abnormality.	-
Berry et al. (15)	9 episodes in 5 pediatric patients	Regimen of modified parenteral nutrition used in 6 occasions (3 times with modified parenteral nutrition and 3 times with modified parents nutrition plus formula)	Effective reduction in leucine levels in all 6 episodes	Severe patients treated immediately with dialysis. Authors reported the value being the simplicity of use of the IV BCAA free formulation.
Thompson et al. (14)	1 newborn	IV amino-acid supplement with low concentration of BCAAs 6 h after haemofiltration	Control achieved within 8 h of haemofiltration	Major treatment was continuous venous haemofiltration.
Townsend et al. (13)	1 newborn	Parenteral nutrition mixture lacking leucine, isoleucine, and valine, supplementedwith Intralipid to provide an average of 125 kcal/kg/day	“Achieves and sustains BCAA removal with fewer risks than multiple exchange transfusions or peritoneal dialysis”	Total parenteral nutrition initiated after patient was unable to continue nasogastric feeding and peritoneal dialysis had failed due to the patient's hypotonia.

BCAA, branched-chain amino acids; IV, intravenous; IV-PN, intravenous dextrose and BCAA-free amino acid mixture; NS, not significant.