PARTIAL BLOCK OF GLYCOLYSIS IN LATE-ONSET PHOSPHOFRUCTOKINASE DEFICIENCY MYOPATHY

A late-onset, myopathic variant of phosphofructokinase (PFK) deficienc y has been previously described in two patients of Ashkenazic descent. We report here on a non-Ashkenazic woman with the onset, at the age o f 48 years, of a progressive limb girdle myopathy that was not precede d by a history of exercise intolerance. Muscle biopsy findings at the age of 58 years showed deposition of amylopectin-like material in musc le fibers and the absence of histochemical PFK activity. Enzymatic PFK activity in vitro was only 4% of normal. Since the forearm ischemic e xercise test induced a sub-normal production of serum lactate, the pat ient underwent phosphorus magnetic resonance spectroscopy (P-31-MRS), a noninvasive method that allows in vivo assessment of the functional status of the glycolytic pathway and mitochondrial oxidative metabolis m by measuring the high-energy phosphates and cytosolic pH. In vivo, P -31-MRS disclosed a residual glycolytic flux and a normal rate of ATP production both at rest and during exercise. These results suggest tha t, in some patients, muscle PFK deficiency may be partial in vivo, and more severe in vitro, possibly due to protein or mRNA instability rat her than absence. The presence of these findings in a patient with the late-onset myopathic form is compatible with a distinct pathogenetic mechanism, relying on progressive polysaccharide accumulation, rather than on acute energetic shortage in muscle fibers.