Reduction of hyperornithinemia with a low protein, low arginine diet and pyridoxine in patients with a deficiency of ornithine-ketoacid transaminase (OKT) activity and gyrate atrophy of the choroid and retina.

Five patients with gyrate atrophy of the choroid and retina showed a 60% of greater decline in plasma ornithine levels during a five week trial of a low protein (10--15 g/day), low arginine (0.50--0.75 g/day) diet supplemented with essential amino acids and pyridoxine administration. These declines in plasma ornithine levels were seen in Patients 1--4 with the pyridoxine non-responsive variant and in Patient 5 with the pyridoxine responsive variant. No harmful systemic side effects were noted. Patients 1--4 continued on a modified low protein (20--35 g/day), low arginine (1.25--1.75 g/day) diet as tolerated and Patient 5 on pyridoxine alone. After one year no improvement was observed in visual acuities, visual fields, final dark adapted thresholds and full field electroretinograms for four patients. In contrast to the other four patients, Patient 3, with relatively poor control of plasma ornithine levels, showed signs of progression of the chorioretinal atrophy and further reduction of electroretinographic responses. Patients 1--4 continue on the dietary regimen and Patient 5 on pyridoxine alone to determine whether any lowering of plasma ornithine levels will modify the course of their ocular disease.

Visual results of a long-term trial of a low-arginine diet in gyrate atrophy of choroid and retina.

Visual function has been serially assessed in two gyrate atrophy patients who have had long-term reduction of plasma ornithine concentrations by a low-arginine diet. One patient demonstrated subjective and objective improvement after 15 months of treatment. In addition to improvements in dark adaptation thresholds, enlargement of visual fields, and a more normal electroretinogram, there was marked improvement in cone function as measured by color vision. There has been no change noted in the second patient. These results suggest that reduction of plasma ornithine may be beneficial in gyrate atrophy patients and that the high ornithine concentrations characteristic of this disorder play some role in the pathophysiology.

Ocular findings in patients with gyrate atrophy on pyridoxine and low-protein, low-arginine diets.

Five patients, ages 12 to 30, with gyrate atrophy have shown substantial (60% or greater) decreases in plasma ornithine concentrations within four to eight weeks when placed on a therapeutic trial of low-protein (10-15 g/day), low-arginine diets supplemented with essential amino acids (EAA) and pyridoxine hydrochloride. Four of five patients have continued on modified protein restriction (20-35 g/day) and one on pyridoxine (300 mg/day) alone with maintenance of plasma ornithine in the range of 30 to 60% below pretherapeutic trial levels. After one year, four of five patients have shown no significant improvement in visual acuity, fields, final dark-adapted thresholds, electroretinograms, or fundus appearance. One patient with the poorest control of plasma ornithine has developed a decrease in ERG amplitudes and a new area of chorioretinal atrophy. These patients continue in this trial to determine whether or not any reductions in hyperornithinemia will modify the course of the ocular disease.

Gyrate atrophy of the choroid and retina. Biochemical considerations and experience with an arginine-restricted diet.

Ornithine-delta-aminotransferase deficiency is the primary biochemical defect in gyrate atrophy of the choroid and retina and results in the characteristic accumulation of ornithine. An additional consequence of this inborn error is that arginine, the precursor of ornithine, becomes an essential amino acid. Therefore, to reduce the accumulated ornithine, we placed nine gyrate atrophy patients on an arginine-restricted diet. Plasma ornithine decreased by 50 to 85% within one month. Orally administered, alpha-aminoisobutyric acid facilitated the reduction in ornithine by augmenting renal losses. Over the long term, three patients have maintained near normal plasma ornithine concentrations from 4 to 32 months. Two patients have maintained less striking reductions in ornithine, and four have either been poorly controlled or have terminated the diet. Urinary losses of arginine and ornithine in gyrate atrophy patients with high or low plasma ornithine concentrations are less than 50% of the estimated arginine intake. This observation suggests that the bulk of ingested arginine is somehow metabolized despite the severe reduction in ornithine-delta-aminotransferase activity.

Gyrate atrophy of the choroid and retina: improved visual function following reduction of plasma ornithine by diet.

In a patient with gyrate atrophy of the choroid and retina, an arginine-deficient diet has reduced plasma ornithine concentration fivefold during the past 20 months. Subjective improvement in her visual function was noted approximately 15 months after institution of her diet. This has been documented by improvements in the electroretinogram, dark-adaptation, and color vision. The improvement involves rod and, to a lesser extent, cone function. The results, although preliminary and limited to a single patient, suggest that reduction of plasma ornithine with a low arginine diet is beneficial in this disease.