Figure 1
Medications used in primary hyperammonaemias
| Medications for acute and long-term use in primary hyperammonaemias | |||
|---|---|---|---|
| Substance | Acute situation | Long-term use | Rationale |
| Sodium benzoate (infusion in 10% dextrose) | 250 mg/kg bw as bolus in 90–120 min, then continuous infusion 250–500 mg/kg/day | 250–500 mg/kg/day | Conjugation with glycine and excretion as non-toxic hippuric acid in urine |
| Sodium phenylbutyrate/ Sodium phenylacetate (infusion in 10% dextrose) | 250 mg/kg bw as bolus in 90–120 min, then continuous infusion 250–500 mg/ kg/day | 250–500 mg/kg/day | Conjugation with glutamine and excretion as non-toxic phenylacetylglutamine in urine |
| Glycerol phenylbutyrate | Not indicated | 8.5 ml/m2/day (9.4 g/m2/day) in patients with body surface <1.3 m2 7 ml/m2/day (8 g/m2/day) in patients with body surface ≥1.3 m2 | Conjugation with glutamine and excretion as non-toxic phenylacetylglutamine in urine; slower release and uptake than sodium PBA |
| L-arginine hydrochloride Contraindicated in arginase deficiency. | 250 mg/kg bw (1.2 mmol/kg) as bolus in 90–120 min, then continuous infusion 250 mg/kg/day | 250 mg/kg/day | To improve the residual function of the urea cycle and avoid arginine deficiency |
| N-carbamyl-glutamate For NAGS deficiency. | 100 mg/kg as oral bolus (or via NG tube), then 25–62.5 mg/kg bw every 6 h | 25–62.5 mg/kg bw every 6 h (taper to the lowest possible dose) | Activation of CPS1 |
Summary of the main biochemical aspects of primary hyperammonaemias
| Primary hyperammonaemia | |||
|---|---|---|---|
| Enzyme defects of the urea cycle | |||
| Disorder | Main diagnostics | Key metabolites | Pathomechanism |
| NAGS deficiency | Amino acids in plasma | Glutamine in plasma increased, | Enzymatic block |
| CPS1 deficiency | Amino acids in plasma | Glutamine in plasma increased, | Enzymatic block |
| OTC deficiency | Amino acids in plasma, orotic acid in urine | Glutamine in plasma increased, | Enzymatic block |
| ASS deficiency | Amino acids in plasma, orotic acid in urine | Glutamine and citrulline in plasma increased, orotic acid in urine increased | Enzymatic block |
| ASL deficiency | Amino acids in plasma, orotic acid in urine | Glutamine, citrulline and argininosuccinate in plasma and urine increased, orotic acid in urine increased | Enzymatic block |
| ARG1 deficiency | Amino acids in plasma | Arginine in plasma increased | Enzymatic block |
| Transporter defects of the urea cycle | |||
| HHH syndrome | Amino acids in plasma and urine | Ornithine in plasma increased, homocitrulline in urine increased | Deficiency of mitochondrial ornithine (substrate of OTC) |
| Citrin deficiency | Amino acids in plasma | Citrulline in plasma increased | Deficiency of cytosolic aspartate (substrate of ASS) |