Genetic aspects in gyrate atrophy of the choroid and retina with hyperornithinaemia.

The relative importance of genetic degenerative eye lesions as causes of blindness or impaired vision has increased because of the lack of effective treatment for such conditions as compared with other diseases. Related to the large and not very well-defined group of degenerative eye lesions termed tapeto-retinal degenerations, is a choroidal form known as gyrate atrophy of the choroid and retina. Night blindness is the most important subjective symptom in hereditary tapeto-retinal degeneration. Sharply-defined chorio-retinal atrophic areas of the fundus are typical of gyrate atrophy. In addition to constriction of the fields of vision, myopia, and complicated cataract, abnormalities in the electroretinogram, electro-oculogram, and fluorescein angiograms of the fundus form the basis for diagnosis. A constant relationship between gyrate atrophy of the choroid and retina and massively increased plasma ornithine concentration was found in our earlier studies (Simell and Takki, 1973; Takki, I974), in which it was suggested that the clinical symptoms and signs of the disease were due to large concentrations of ornithine in the plasma, aqueous humour, and cerebrospinal fluid or directly to the causative enzyme defect. Though gyrate atrophy of the choroid and retina is a relatively rare ophthalmological disease and the published series of patients are small, inheritance has been suggested. Consanguinity of the parents, familial occurrence, and sporadic cases have been described (Cutler, I895; McGuire, I932; McGuire and McGuire, 194I; Waardenburg, 1939; Davis and Sheppard, 1940; Malbran and Fonte, 1947; Fran,ois, Barbier, and de Rouck, I959; Kurstjens, I965; Rieger, 1972; Botermans, 1972), but autosomal inheritance now seems to be a probable cause (Kurstjens, I965; Botermans, I972). The combination ofclinical symptoms with inborn errors ofmetabolismwas not understood until some relatives of the propositi were found to have the metabolic abnormality without the clinical disease (Ghadimi, Partington, and Hunter, I 96 I; Woody, Hutzler, and Dancis, I 966; Auerbach, DiGeorge, and Carpenter, I967). The aim of this work was to confirm the regular combination of massively increased plasma ornithine concentration with the ophthalmological symptoms and signs by studying the eyes and plasma and/or urinary amino-acids of relatives of the patients, to test the autosomal recessive mode of inheritance in this group of families, and to find a clinical method for heterozygote detection in hyperornithinaemia by studying ornithine metabolism in probable heterozygotes of the disease and in controls.