›20–120 mg/kg/day
›Prevents secondary deficiency during leucine crisis
›Target plasma isoleucine 400–800 µmol/L
›Valine IV or enteral
›20–120 mg/kg/day
›Target plasma valine 400–800 µmol/L
›Rationale
›Leucine crisis depletes isoleucine and valine
›Deficiency impairs protein synthesis and worsens encephalopathy
›Supplementation sustains anabolic state
Cerebral edema management
›Osmotherapy
›Mannitol
›0.5–1 g/kg IV over 20 minutes
›Repeat every 4–6 hours as needed
›Monitor serum osmolality — stop if >320 mOsm/kg
›Hypertonic saline 3%
›2–3 mEq/kg IV over 20–30 minutes
›Preferred when hyponatremia is contributing
›Maintains sodium 138–145 mEq/L
›Furosemide adjunct
›0.5–1 mg/kg IV
›Used with mannitol to augment osmotic effect
›Monitor electrolytes
›ICP precautions
›Head of bed 30 degrees
›Midline head position
›Avoid neck flexion
›Normoventilation
›Target PaCO2 35–40 mmHg unless herniation imminent
›Avoid hyperventilation except for acute herniation rescue
›Avoid hypotonic fluids
›Hypotonic IV worsens hyponatremia and cerebral edema
›All fluids to be isotonic or hypertonic
Sodium phenylbutyrate (emerging adjunct)
›Sodium phenylbutyrate role
›Leucine-lowering adjunct
›Reported leucine reduction rate ~530 µmol/L at 24 hours
›Acts via nitrogen scavenging and metabolic diversion
›Not yet standard of care
›Emerging evidence; use guided by metabolic specialist
›Dosing per specialist recommendation
›First-line anticonvulsants
›Benzodiazepines for active seizure
›Lorazepam 0.05–0.1 mg/kg IV (max 4 mg per dose)
›Midazolam 0.1 mg/kg IV or 0.2 mg/kg intranasal
›Phenobarbital for refractory seizures
›20 mg/kg IV loading dose over 20 minutes
›Maintenance 3–5 mg/kg/day
›Note: seizures may not fully respond until leucine decreases
›Metabolic correction is primary anticonvulsant strategy
›Empiric antibiotic strategy
›Low threshold for empiric coverage when infectious trigger suspected
›Fever, elevated WBC, or indwelling central line
›Do not delay metabolic treatment for cultures
›Empiric regimen selection
›Neonates: ampicillin + gentamicin +/- acyclovir
›Older children: ceftriaxone 50–75 mg/kg/day IV
›Candida risk with central line: fluconazole 6–12 mg/kg IV
›De-escalate based on culture results and clinical response
›Avoid prolonged broad-spectrum exposure
›Renal replacement therapy indications
›Leucine not declining despite maximal anabolic therapy
›Escalating encephalopathy or cerebral edema
›Leucine >1500 µmol/L unresponsive to 12–24 hours of treatment
›CRRT technique
›Preferred over intermittent HD in hemodynamically unstable patients
›Leucine is highly dialyzable (molecular weight 131 Da)
›Can accelerate leucine clearance substantially
›Continue anabolic therapy during dialysis
›Dextrose and BCAA-free amino acids continue concurrently
›Monitor isoleucine and valine closely — may be dialyzed off