Use of an Arginine-Restricted Diet to Slow Progression of Visual Lossin Patients With Gyrate Atrophy

Abstract

To quantify the effect of long-term reduction of plasma ornithine levels through adherence to an arginine-restricted diet on visual function in patients of all ages with gyrate atrophy of the retina and choroid.Methods: A long-term observational study was conducted on 27 patients with gyrate atrophy, 17 of whom elected to comply with the arginine-restricted diet and 10 who were unable to comply. The mean rates of change in the electroretinogram combined response, electroretinogram flicker response, and kinetic and static perimetry were determined.Results: After mean follow-up of 13.9 years for the pa-tients on the diet and 14.1 years for those not on the diet, the mean rates of change for the diet group compared with those of the no-diet group were statistically significantly slower for all outcome measures (age-adjusted PϽ.05) except for static perimetry (P=.06). Conclusions:Adhering to an arginine-restricted diet so as to lower the plasma ornithine level below an average of 5.29 to 6.61 mg/dL (400-500 µmol/L) will slow the loss of function as measured by sequential electroretinography and visual field examinations.

Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model

“… 26 , 27 , 54 , 55 No adverse effects were reported in limiting arginine in the diet. 56 In our study, arginine depletion in mice had no visible effect on mice litter size, offspring weight, or kidney-to-body weight ratio. However, other side effects of arginine depletion during pregnancy can be detected at later stages and need further investigation.…”

Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model

“… 26 , 27 , 54 , 55 No adverse effects were reported in limiting arginine in the diet. 56 In our study, arginine depletion in mice had no visible effect on mice litter size, offspring weight, or kidney-to-body weight ratio. However, other side effects of arginine depletion during pregnancy can be detected at later stages and need further investigation.…”

Regression of treatment-resistant gyrate atrophy-associated intraretinal cystic spaces using long-term diet restriction: A case report

“…Several interventions have been reported for the treatment of GA-associated ICS including the use of arginine-restricted diets, vitamin B6 supplementation, IVB, CAIs, and NSAIDs. 4–8 Importantly, all these modalities were used in our patient, but only prolonged dietary modifications gave consistent results. Previously, Kaiser-Kupfer et al studied a group of 27 patients with gyrate atrophy; of these, 17 (mean age = 13.9 years) followed an arginine-restricted diet and 10 (mean age 14.1) were unable to do so.…”

“…Previously, Kaiser-Kupfer et al studied a group of 27 patients with gyrate atrophy; of these, 17 (mean age = 13.9 years) followed an arginine-restricted diet and 10 (mean age 14.1) were unable to do so. 4 The target plasma ornithine level was below 400−500 μmol/L. Using electroretinogram, combined and flicker responses, and Goldmann kinetic perimetry as outcome measures, that study found that an arginine-restricted diet significantly slowed loss of function in patients.…”

Auxotrophy-Based Detection of Hyperornithinemia in Mouse Blood and Urine

“…In addition to early institution of the highly restrictive diet, rigorous compliance is also required to successfully maintain, over the long term, a chronic reduction in plasma ornithine. Although our assays were not able to detect blood ornithine at concentrations near normal physiological levels (about 40-120 µmol/L 9,20 ), blood levels under 400 to 500 μmol/L are generally considered therapeutic. 20 Thus, our method, as described, appears to provide a range of sensitivity that would allow patients with GACR to routinely monitor their blood levels of ornithine, facilitating their better maintenance of optimum biochemical control.…”

Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model

“… 26 , 27 , 54 , 55 No adverse effects were reported in limiting arginine in the diet. 56 In our study, arginine depletion in mice had no visible effect on mice litter size, offspring weight, or kidney-to-body weight ratio. However, other side effects of arginine depletion during pregnancy can be detected at later stages and need further investigation.…”

Regression of treatment-resistant gyrate atrophy-associated intraretinal cystic spaces using long-term diet restriction: A case report

“…Several interventions have been reported for the treatment of GA-associated ICS including the use of arginine-restricted diets, vitamin B6 supplementation, IVB, CAIs, and NSAIDs. 4–8 Importantly, all these modalities were used in our patient, but only prolonged dietary modifications gave consistent results. Previously, Kaiser-Kupfer et al studied a group of 27 patients with gyrate atrophy; of these, 17 (mean age = 13.9 years) followed an arginine-restricted diet and 10 (mean age 14.1) were unable to do so.…”

“…Previously, Kaiser-Kupfer et al studied a group of 27 patients with gyrate atrophy; of these, 17 (mean age = 13.9 years) followed an arginine-restricted diet and 10 (mean age 14.1) were unable to do so. 4 The target plasma ornithine level was below 400−500 μmol/L. Using electroretinogram, combined and flicker responses, and Goldmann kinetic perimetry as outcome measures, that study found that an arginine-restricted diet significantly slowed loss of function in patients.…”

Auxotrophy-Based Detection of Hyperornithinemia in Mouse Blood and Urine

“…In addition to early institution of the highly restrictive diet, rigorous compliance is also required to successfully maintain, over the long term, a chronic reduction in plasma ornithine. Although our assays were not able to detect blood ornithine at concentrations near normal physiological levels (about 40-120 µmol/L 9,20 ), blood levels under 400 to 500 μmol/L are generally considered therapeutic. 20 Thus, our method, as described, appears to provide a range of sensitivity that would allow patients with GACR to routinely monitor their blood levels of ornithine, facilitating their better maintenance of optimum biochemical control.…”

Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model

“… 26 , 27 , 54 , 55 No adverse effects were reported in limiting arginine in the diet. 56 In our study, arginine depletion in mice had no visible effect on mice litter size, offspring weight, or kidney-to-body weight ratio. However, other side effects of arginine depletion during pregnancy can be detected at later stages and need further investigation.…”

Regression of treatment-resistant gyrate atrophy-associated intraretinal cystic spaces using long-term diet restriction: A case report

“…Several interventions have been reported for the treatment of GA-associated ICS including the use of arginine-restricted diets, vitamin B6 supplementation, IVB, CAIs, and NSAIDs. 4–8 Importantly, all these modalities were used in our patient, but only prolonged dietary modifications gave consistent results. Previously, Kaiser-Kupfer et al studied a group of 27 patients with gyrate atrophy; of these, 17 (mean age = 13.9 years) followed an arginine-restricted diet and 10 (mean age 14.1) were unable to do so.…”

“…Previously, Kaiser-Kupfer et al studied a group of 27 patients with gyrate atrophy; of these, 17 (mean age = 13.9 years) followed an arginine-restricted diet and 10 (mean age 14.1) were unable to do so. 4 The target plasma ornithine level was below 400−500 μmol/L. Using electroretinogram, combined and flicker responses, and Goldmann kinetic perimetry as outcome measures, that study found that an arginine-restricted diet significantly slowed loss of function in patients.…”

Auxotrophy-Based Detection of Hyperornithinemia in Mouse Blood and Urine

“…In addition to early institution of the highly restrictive diet, rigorous compliance is also required to successfully maintain, over the long term, a chronic reduction in plasma ornithine. Although our assays were not able to detect blood ornithine at concentrations near normal physiological levels (about 40-120 µmol/L 9,20 ), blood levels under 400 to 500 μmol/L are generally considered therapeutic. 20 Thus, our method, as described, appears to provide a range of sensitivity that would allow patients with GACR to routinely monitor their blood levels of ornithine, facilitating their better maintenance of optimum biochemical control.…”