ISOLATED PERSISTENT HYPERMETHIONINEMIA

New information has been obtained on 30 patients with isolated persist ent hypermethioninemia, most of them previously unreported. Biopsies t o confirm the presumptive diagnosis of partially deficient activity of ATP: L-methionine S-adenosyltransferase (MAT; E.C.2.5.1.6) in liver w ere not performed on most of these patients. However, none showed the clinical findings or the extreme elevations of serum folate previously described in other patients with isolated hypermethioninemia consider ed not to have hepatic MAT deficiency. Patients ascertained on biochem ical grounds had no neurological abnormalities, and 27/30 had IQs or B ayley development-index scores within normal limits or were judged to have normal mental development. Methionine transamination metabolites accumulated abnormally only when plasma methionine concentrations exce eded 300-350 mu M and did so more markedly after 0.9 years of age. Dat a were obtained on urinary organic acids as well as plasma creatinine concentrations. Patterns of inheritance of isolated hypermethioninemia were variable. Considerations as to the optimal management of this gr oup of patients are discussed.