Isolated Persistent Hypermethioninemia

Summary Newinformation hasbeen obtained on30patients with isolated persistent hypermethioninemia, mostofthem previously unreported. Biopsies toconfirm thepresumptive diagnosis ofpartially deficient activity ofATP: L-methionine S-adenosyltransferase (MAT;E.C.2.5.1.6) inliver werenotperformed onmostofthese patients. However, noneshowed theclinical findings ortheextreme elevations ofserum folate previously described in other patients with isolated hypermethioninemia considered nottohavehepatic MAT deficiency. Patients ascertained onbiochemical grounds hadnoneurological abnormalities, and27/30 hadIQsorBayley developmentindex scores within normal limits orwerejudged tohave normal mental development. Methionine transaminationmetabolites accumulated abnormally onlywhen plasma methionine concentrations exceeded 300-350 tiManddidsomoremarkedly after 0.9years ofage. Datawereobtained onurinary organic acids aswell as plasma creatinine concentrations. Patterns ofinheritance ofisolated hypermethioninemia werevariable. Considerations astotheoptimal management ofthis group ofpatients arediscussed.