Gyrate atrophy of the choroid and retina: Lymphocyte ornithine-δ- aminotransferase activity in different mutations and carriers

Deficiency of ornithine-δ-aminotransferase (OAT) causes gyrate atrophy of the choroid and retina with hyperornithinemia (GA; McKusick 258870), a progressive autosomal recessive chorioretinal degeneration leading to early blindness. As residual enzyme activity may vary in different mutations of the OAT gene and explain individual variations in disease progression, a sensitive HPLC modification of the OAT assay in lymphocytes was developed, based on measurement of the dihydroquinozolinium reaction product. The OAT activities (ranges) of 43 Finnish GA patients with mutations L402P/L402P, R180T/L402P, N89K/LA02P, and LA02P/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) pmol·min^-1 mg protein^-1. This lymphocyte assay is an easy, rapid, and sensitive method for reliable recognition of GA homozygotes. OAT mutations of the Finnish patients show similar residual enzyme activity in the lymphocytes. OAT activities in the L402P heterozygotes and healthy control subjects overlap, suggesting that, for reliable carrier detection, the OAT alleles have to be studied. However, as all OAT mutations are not known, direct measurement of enzyme activity has a role in heterozygote identification and possibly also in prenatal diagnosis of GA.