LATE-ONSET MUSCLE WEAKNESS IN PARTIAL PHOSPHOFRUCTOKINASE DEFICIENCY - A UNIQUE MYOPATHY WITH VACUOLES, ABNORMAL MITOCHONDRIA, AND ABSENCE OF THE COMMON EXON-5 INTRON-5 JUNCTION POINT MUTATION
K. Sivakumar et al., LATE-ONSET MUSCLE WEAKNESS IN PARTIAL PHOSPHOFRUCTOKINASE DEFICIENCY - A UNIQUE MYOPATHY WITH VACUOLES, ABNORMAL MITOCHONDRIA, AND ABSENCE OF THE COMMON EXON-5 INTRON-5 JUNCTION POINT MUTATION, Neurology, 46(5), 1996, pp. 1337-1342
Three patients (ages 51, 59, and 79) from two generations of an Ashken
azi Jewish family had partial (33% activity) phosphofructokinase (PFK)
deficiency that presented with fixed muscle weakness after the age of
50 years. MR spectroscopy revealed accumulation of phosphomonoesters
during exercise. Muscle biopsy showed a vacuolar myopathy with increas
ed autophagic activity and several ragged-red and cytochrome c oxidase
-negative fibers. The older patient, age 79 at biopsy, had several nec
rotic fibers. Electron microscopy revealed subsarcolemmal and intermyo
fibrillar glycogen accumulation and proliferation of mitochondria with
paracrystalline inclusions, probably related to reduced availability
of energy due to impaired glycolysis. The common point mutation of exo
n 5/intron 5 junction seen in Jewish Ashkenazi patients with PFK defic
iency was excluded. We conclude that late-onset fixed muscle weakness
occurs in partial PFK deficiency and it may represent the end result o
f continuing episodes of muscle fiber destruction. Partial enzyme defi
ciency in two successive generations suggests a unique molecular mecha
nism.