Highly Elevated Plasma γ-Glutamyltransferase Elevations: A Trait Caused by γ-Glutamyltransferase 1 Transmembrane Mutations

Assay of γ‐glutamyltransferase (GGT) activity is a widely used test to indicate and monitor liver and biliary tract injury. We observed dominant inheritance of highly elevated plasma GGT levels, designated GGTemia, in two unrelated families. Neither clinical symptoms nor alterations of GGT substrates were associated with GGTemia. A plasma GGT fraction pattern distinguishes this trait from common liver diseases. Heterozygous γ‐glutamyltransferase 1 (GGT1) mutations that disrupt the GGT1 transmembrane domain were identified. We establish GGTemia as a benign condition; GGT1 mutation testing can prevent repeated and invasive diagnostic workup in such patients.