title: Late-onset muscular weakness in phosphofructokinase deficiency due to exon 5/intron 5 junction point mutation: a unique disorder or the natural course of this glycolytic disorder?
abstract: Late-onset muscle weakness is rare in glycolytic disorders. There are two reports in the literature of phosphofructokinase (PFK)-deficient Ashkenazi Jews with severe vacuolar myopathy manifesting in late adulthood. The genetic abnormality in these patients is unknown. We report a third patient with a similar syndrome: early-onset exercise intolerance in young childhood and progressive weakness in a limb-girdle distribution appearing at 57 years of age, leading to severe incapacity. Muscle histology showed diffuse vacuolar changes, and muscle fibers contained excess glycogen-like material. Muscle biochemistry was diagnostic for PFK deficiency. DNA analysis from the patient and his family showed 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 members were heterozygous for this mutation. It is not clear whether late-onset weakness is the natural course for all PFK-deficient patients or whether the exon 5 mutation carries increased risk for this severe myopathy.
authors.affiliation: Department of Neurology, Hebrew University--Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Argov
authors.forename: V
authors.initials: V
authors.lastname: Barash
authors.forename: D
authors.initials: D
authors.lastname: Soffer
authors.forename: J
authors.initials: J
authors.lastname: Sherman
authors.forename: N
authors.initials: N
authors.lastname: Raben
mesh_terms: D001483:Base Sequence; D005091:Exons; D006019:Glycolysis; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000201:enzymology* / Q000235:genetics*; D010732:Phosphofructokinase-1 / Q000172:deficiency* / Q000235:genetics; D017354:Point Mutation
chemical_list: D010732:Phosphofructokinase-1