GYRATE ATROPHY OF THE CHOROID AND RETINA - LYMPHOCYTE ORNITHINE-DELTA-AMINOTRANSFERASE ACTIVITY IN DIFFERENT MUTATIONS AND CARRIERS

Deficiency of ornithine-delta-aminotransferase (OAT) causes gyrate atr ophy of the choroid and retina with hyperornithinemia (GA; McKusick 25 8870), a progressive autosomal recessive chorioretinal degeneration le ading to early blindness. As residual enzyme activity may vary in diff erent mutations of the OAT gene and explain individual variations in d isease progression, a sensitive HPLC modification of the OAT assay in lymphocytes was developed, based on measurement of the dihydroquinozol inium reaction product. The OAT activities (ranges) of 43 Finnish GA p atients with mutations L402P/L402P, R180T/L402P, N89K/ L402P, and LA02 P/x (x = previously unknown allele), were <1-10, <1-13, <1-17, and <1 pmol.min(-1) mg protein(-1), respectively. The OAT activities (mean +/ - SD) of nine L402P/ wild heterozygotes were 70 +/- 50 (range 33-193), and those of 15 healthy control subjects 184 +/- 60 (range 85-291) pm ol.min(-1) mg protein(-1). This lymphocyte assay is an easy, rapid, an d sensitive method for reliable recognition of GA homozygotes. OAT mut ations of the Finnish patients show similar residual enzyme activity i n the lymphocytes. OAT activities in the LA02P heterozygotes and healt hy control subjects overlap, suggesting that, for reliable carrier det ection, the OAT alleles have to be studied. However, as all OAT mutati ons are not known, direct measurement of enzyme activity has a role in heterozygote identification and possibly also in prenatal diagnosis o f GA.