Arginase 1 deficiency: long-term follow-up of the original patients

Arginase 1, the enzyme responsible for the last step of the urea cycle, catalyzes the hydolysis of arginine to urea and ornithine. In contrast to other urea cycle defects, its deficiency usually does not cause early and catastrophic hyperammonemia. Instead, this extremely rare disease typically presents with progressive cerebral and motoneuron disorder (spastic paraplegia and seizures) and/or a hepatic phenotype with neonatal cholestasis, acute liver failure, or liver fibrosis, making it a prime example of how pathology in the liver affects other organs.

The underlying pathogenetic mechanisms have not been fully understood yet. However, the accumulation of arginine and consecutive abnormalities in the metabolism of guanidino compounds and nitric oxide are thought to be involved in pathophysiological processes in the CNS. In addition, induction of arginase 2 enzyme function may be involved in the pathogenesis of liver disease in arginase 1 deficiency.

Treatment of arginase 1 deficiency resembles that of other UCDs and consists of a strict restriction of protein intake to reduce arginine levels and of nitrogen scavenging drugs to prevent hyperammonemia but often cannot prevent disease progression.

We provide clinical data on the long-term follow-up of the first patients ever described with this extremely rare disorder of the urea cycle.

Corresponding author: Schlune, Andrea

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