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

Expert Review of Endocrinology & Metabolism
Johannes Häberle

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.

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