Atypical Gyrate Atrophy of Retina and Iminoglycinuria TAKASHI SAITO

Tohoku J. exp. Med., 1981, 135, 331-332

Short Report

Atypical Gyrate Atrophy of the Choroid and Retina and Iminoglycinuria

TAKASHI SAITO, SEIJI HAYASAKA,*KAZUYUKI YABATA,* KIYOSHIOMURA, KATSUYOSHI MIZUNO* and KEIYA TADA Departments of Pediatrics and *ophthalmology, Tohoku University School of Medicine, Sendai 980

SAITO, T., HAYASAKA, S., YABATA, K., OMURA, K., MIzuwo, K. and TADA, K. Atypical Gyrate Atrophy of the Choroid and Retina and Iminoglycinuria. Tohoku J. exp. Med., 1981, 135 (3), 331-332 A 44-year-old woman with atypical gyrate atrophy and iminoglycinuria was described. The serum ornithine level and ornithine-ketoacid transaminase (OKT) activity were both normal. Urinary excretion of proline, hydroxyproline and glycine was markedly increased. This finding, together with the existence of gyrate atrophy with hyperornithinemia due to OKT deficiency, suggests that proline deficiency in the chorioretinal tissues may concern the development of gyrate atrophy. - chorioretinal atrophy; hyperornithinemia; iminoglycinuria; proline

Gyrate atrophy is a rare, inherited disease of chorioretinal atrophy. The plasma level of ornithine was found to be increased in affected patients (Simell and Takki 1973), and OKT in cultured skin fibroblasts was deficient in these patients. However, the mechanism of the ocular disturbance is still obscure because other patients with a similar degree of hyperornithinemia have no ocular problems (Gatfield et al. 1975) and there are cases of gyrate atrophy without hyperornithinemia (Jaeger et al. 1979). Recently we had a peculiar case which showed fundus changes similar to gyrate atrophy but lacked hyperornithinemia and in which urinary concentrations of iminoacids and glycine were markedly increased.

PATIENT AND METHODS

The patient was a 44-year-old woman whose parents were first cousins, and had a 5-year history of night blindness. She was referred to our University Hospital because of progressive visual disturbances. Ophthalmologic examination revealed myopia, dark blindness, constricted visual fields and chorioretinal atrophy in both eyes. Characteristic lesions resembling gyrate atrophy were noted at the lower periphery (Fig. 1). Serum and urinary amino acid levels were measured on a Hitachi amino acid analyzer (type 835). OKT activity in cultured skin fibroblasts was determined by spectrophoto- metric methods (Katsunuma et al. 1964).

RESULTS AND DISCUSSION All of the routine laboratory tests showed normal values. The serum ornithine level was 1.51 mg/100 ml (normal 0.36-1.56 mg/100 ml) and other serum amino acid levels were also within normal range. OKT activity in cultured skin fibroblasts was 178 nmoles/mg protein/hr (normal controls: 182±8 nmoles/mg protein/hr). Received for publication, March 12, 1981. 331 332 T. Saito et al.

Fig. 1. Ophthalmoscopic finding of the patient.

TABLE 1. Endogeneous renal clearance of amino acids

Amino acid analysis of urine showed a marked increase in iminoacids and glycine excretion; excreted proline content was 108 mg/day, hydroxyproline 36 mg/day and glycine 581 mg/day (Table 1). Iminoglycinuria (prolinuria) is known to be due to a defect in transport of iminoacids and glycine in the renal tubule (Tada et al. 1965). A large amount of proline is excreted in the urine in affected patients. In the patients with typical gyrate atrophy and hyperornithinemia, ornithine catabolism to proline is disturbed due to the deficiency of OKT. These observations suggest that a deficiency of proline in the chorioretinal tissues may concern the development of gyrate atrophy.

References 1) Gatfield, P.D., Taller, E., Wolfe, D.M. & Haust, M.D. (1975) Hyperornithinernia, hyperammonemia and homocitrullinuria associated with decreased carbamyl phosphate synthetase I activity. Pediat. Res., 9, 488-497. 2) Jaeger, W., Kettler, J.V., Luty, P. & Hilsdorf, C. (1979) Differential diagnosis of gyrate atrophy of the choroid and retina. Metab. Pediat. Ophthal., 3, 189-191. 3) Katsunuma, N., Matsuda, Y. & Tomino, I. (1964) Studies on ornithine-ketoacid tran saminase. J. Biochem., 56, 499-503. 4) Simell, 0. & Takki, K. (1973) Raised plasma-ornithine and gyrate atrophy of the choroid and retina. Lancet, 1, 1031-1033. 5 ) Tada, K., Morikawa, T., Ando, T., Yoshida, T. & Minagawa , A. (1965) A new tubular defect in transport of proline and glycine. T ohoku J. exp . Med., 87, 133-143.