Carglumic acid for the treatment of N-acetylglutamate synthase deficiency and acute hyperammonemia

Abstract

Carglumic acid is a structural analog and the first registered synthetic form of the naturally occurring allosteric activator of the urea cycle, N-acetylglutamate (NAG), which is the product of the enzyme NAG synthase (NAGS). Because NAG is essential for the function of carbamoylphosphate synthetase 1 as the first step of the urea cycle, a decreased availability of NAG due to primary or secondary defects of NAGS will affect ammonia detoxification in the urea cycle. Carglumic acid (Carbaglu®, Orphan Europe SARL, Paris, France) is approved for the acute and long-term treatment of primary defects of NAGS in Europe and the USA. In addition, it is approved in Europe for the treatment of acute hyperammonemia in patients with specific organic acidurias that can lead to NAG deficiency secondary to inhibition of NAGS. This article reviews the use of carglumic acid for both approved indications and considers the potential of this compound for acute hyperammonemias in general.

Keywords::

• carbamylglutamate
• carglumic acid
• hyperammonemia
• isovaleric aciduria
• methylmalonic aciduria
• NAGS deficiency
• N-acetylglutamate synthase deficiency
• N-carbamyl-L-glutamate
• organic acidurias
• propionic aciduria

Financial & competing interests disclosure

The author has been an invited speaker at scientific conferences organized by Orphan Europe and has received travel support for this. Moreover, the author holds a contract with Orphan Europe for conducting molecular genetic investigations in patients with a suspicion of N-acetylglutamate synthase or CPS1 deficiencies. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.