LATE-ONSET MUSCULAR WEAKNESS IN PHOSPHOFRUCTOKINASE DEFICIENCY DUE TOEXON-5 INTRON-5 JUNCTION POINT MUTATION - A UNIQUE DISORDER OR THE NATURAL COURSE OF THIS GLYCOLYTIC DISORDER/

Late-onset muscle weakness is rare in glycolytic disorders. There are two reports in the literature of phosphofructokinase (PFK)-deficient A shkenazi Jews with severe vacuolar myopathy manifesting in late adulth ood. The genetic abnormality in these patients is unknown. We report a third patient with a similar syndrome: early-onset exercise intoleran ce in young childhood and progressive weakness in a limb-girdle distri bution appearing at 57 years of age, leading to severe incapacity. Mus cle histology showed diffuse vacuolar changes, and muscle fibers conta ined excess glycogen-like material. Muscle biochemistry was diagnostic for PFK deficiency. DNA analysis from the patient and his family show ed that he was homozygous for a recently identified point mutation at the exon 5/intron 5 junction (a G-to-A change); two other family membe rs were heterozygous for this mutation. it is not clear whether late-o nset weakness is the natural course for all PFK-deficient patients or whether the exon 5 mutation carries increased risk for this severe myo pathy.