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?

Neurology. 1994 Jun;44(6):1097-100. doi: 10.1212/wnl.44.6.1097.

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.

Publication types

  • Case Reports

MeSH terms

  • Base Sequence
  • Exons
  • Glycolysis
  • Humans
  • Introns
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Muscular Diseases / enzymology*
  • Muscular Diseases / genetics*
  • Phosphofructokinase-1 / deficiency*
  • Phosphofructokinase-1 / genetics
  • Point Mutation*

Substances

  • Phosphofructokinase-1