Enzyme replacement therapy in a patient with hyperargininemia.

Abstract

In a patient with hyperargininemia, enzyme replacement therapy such as whole blood exchange transfusion or erythrocyte transfusion was performed, and its effect was confirmed in vitro as well as in vivo. The patient has been treated with the restriction of protein intake, oral administration of an essential amino acid mixture, and sodium benzoate or phenylacetic acid. With these treatments, his plasma ammonia levels were controlled.On the other hand, plasma and CSF concentrations of arginine were not so well controlled. With whole blood exchange transfusion and erythrocyte transfusion, plasma arginine concentrations and plasma ammonia levels were controlled.These effects have continued for about 3 months. Furthermore, the effect of exchanged erythrocytes on the blood arginine levels was also confirmed by in vitro experimentation that mixes arginine with erythrocytes in the medium RPMI 1640. Arginine concentration of the medium did not decrease when arginine was mixed with erythrocytes of the patient, but when arginine was mixed with erythrocytes of mother or normal controls, it decreased rapidly.In calculation, 10' of erythrocytes of the mother or normal controls was presumed to metabolize 4-5 nmole of arginine per day. From these results, the erythrocyte exchange transfusion is considered to be effective for the control of clinical and biochemical abnormalities in this disorder.blood exchange transfusion ; enzyme replacement therapy ; erythrocyte transfusion ; hyperargininemia

Suggested guidelines for the diagnosis and management of urea cycle disorders

“…Prior attempts have been based on the use of virus-encoded [261] or erythrocyte-contained arginase [262,263]. Frequent blood transfusions help to almost normalize plasma arginine [263] and might be useful for gaining time in order to start definitive therapy [262].…”

“…Prior attempts have been based on the use of virus-encoded [261] or erythrocyte-contained arginase [262,263]. Frequent blood transfusions help to almost normalize plasma arginine [263] and might be useful for gaining time in order to start definitive therapy [262]. However, pegylated human recombinant arginase 1 (PEG-BCT-100) is now available and is being used in a clinical trial for cancer ( http://clinicaltrials.gov/ct2/show/NCT00988195), opening the way to potential testing of its efficacy in ARG1D.…”

Mutations and common variants in the human arginase 1 (ARG1) gene: Impact on patients, diagnostics, and protein structure considerations

“…ARGD is amenable to enzyme replacement due to the fact that it catalyzes a hydrolytic reaction. Initial attempts were done using arginase‐containing erythrocytes (Mizutani, Hayakawa, Maehara, & Watanabe, ; Sakiyama et al., ), achieving almost normalized plasma arginine levels. Later, the effects of pegylated human recombinant ARG1 in a phase 2 clinical trial for liver cancer (https://clinicaltrials.gov/ct2/show/NCT02089763) (Tsui et al., ) were evaluated.…”

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

“…Transfusion of whole blood or erythrocytes has been shown to improve plasma levels of l-arginine and ammonia for a period of up to about 3 months and also to a clinical improvement (Mizutani et al 1987a;Jain-Ghai et al 2011;Sakiyama et al 1984), even though the first report of a trial of enzyme replacement therapy using erythrocyte transfusions showed discouraging results with no significant decrease of blood arginine or clinical improvement (Michels and Beaudet 1978). The positive effect is probably due to the presumed activity of arginase 1 in transfused red blood cells which is well studied in the context of posttransfusional immunosuppression (Bernard et al 2007).…”