Carglumic acid: an additional therapy in the treatment of organic acidurias with hyperammonemia?

Virginie Levrat,Christine Vianey-Saban,Nathalie Guffon,Cécile Acquaviva,Alain Fouilhoux,Isabelle Forest

doi:10.1186/1750-1172-3-2

Abstract

BackgroundHyperammonemia in patients with methylmalonic aciduria (MMA) and propionic aciduria (PA) is caused by accumulation of propionyl-CoA which decreases the synthesis of N-acetyl-glutamate, the natural activator of carbamyl phosphate synthetase 1. A treatment approach with carglumic acid, the structural analogue of N-acetyl-glutamate, has been proposed to decrease high ammonia levels encountered in MMA and PA crises.Case presentationWe described two patients (one with MMA and one with PA) with hyperammonemia at diagnosis. Carglumic acid, when associated with standard treatment of organic acidurias, may be helpful in normalizing the ammonia level.ConclusionEven though the usual treatment which decreases toxic metabolites remains the standard, carglumic acid could be helpful in lowering plasma ammonia levels over 400 micromol/L more rapidly.

Highlights

Hyperammonemia in patients with methylmalonic aciduria (MMA) and propionic aciduria (PA) is caused by accumulation of propionyl-CoA which decreases the synthesis of Nacetyl-glutamate, the natural activator of carbamyl phosphate synthetase 1
We have reported 2 cases of first occurrence of PA and MMA with hyperammonemia who received standard treatment and carglumic acid in addition
Neurological complications are frequently seen in patients with organic acidurias due to deleterious effect of toxic metabolites [4]

Summary

Background

Hyperammonemia in organic acidurias Organic acidurias such as methylmalonic aciduria (MMA) and propionic aciduria (PA) are autosomal recessive disorders of branched-chain amino acid metabolism. A treatment approach with carglumic acid, the structural analogue of N-acetyl-glutamate, has been proposed to decrease high ammonia levels encountered in MMA and PA crises [2,3]. Laboratory studies showed metabolic acidosis (pH 7.1; bicarbonates 9 mmol/L) with massive ketonuria and hyperammonemia (427 micromol/L). Diagnosis of MMA was confirmed by urinary organic acid analysis (methylmalonic acid 20,000 mmol/mol creatinine). Ammonia decreased to 153 micromol/L within 12 h and normalized within 3.5 days, whereas methylmalonic acid excretion decreased more slowly (figure 1). Case 2 The second patient, a girl born in November 1997, presented hypotonia, seizures, poor feeding, dehydration, polypnea at 8 days of age after a symptom-free interval. Laboratory investigations revealed metabolic acidosis (pH 7; bicarbonates 3 mmol/L) with massive ketonuria and hyperammonemia (213 micromol/L). Ammonia was normalized within 36 h, whereas methylcitrate excretion remained elevated (figure 2)

Conclusion

Findings

Butterworth RF