1. Background

• phosphofructokinase (PFK) transforms fructose-6-phosphate to fructose-1,6-diphosphate
• muscle PFK is a homogeneous tetramer containing only the M subunit while erythrocyte PFK is a heterogeneous tetramer containing both M and L (liver) subunits

2. Genetic Defect

• mutation of PFK gene -> abnormal M subunit -> abnormal PFK protein -> inability of muscle and erythrocytes to breakdown glucose to pyruvate or lactate
• a congenital absence of the M subunit results in:
  • muscle - myopathy
  • erythrocytes - causes a hemolytic tendency which produces reticulocytes and a mild polycythemia and increases the production of bilirubin to cause a recurrent jaundice
• an unstable M subunit may be associated with the late appearance of a myopathy

1. Muscle Biopsy

• modest accumluation of glycogen
• PAS-staining deposits beneath the sarcolemma

1. Musculoskeletal Manifestations

• symptoms similar to those of McArdle Disease:
  • temporary weakness and cramping of muscle after exercise
  • exercise intolerance and fatiquability
  • normal motor development

2. Complications (with prolonged vigorous exercise)

• gross myoglobinuria due to rhabdomyolysis resulting in:
  • acute renal failure (for acute episodes)
  • chronic renal failure (for prolonged or frequent repetitive episodes of myoglobinuria)
• gout
• recurrent jaundice
• normal mental development

1. Diagnosis

• decreased PFK activity in erythrocytes (50% of normal) or muscle biopsy biochemistry (<50% of normal)

2. Ischemic Exercise (Lactate) Test

• results similar to those found in McArdle Disease (i.e., reduced or absent rise in blood lactate)

3. Serum

• increased reticulocytes, mild polycythemia, no anemia
• elevated CPK at rest
• elevated bilirubin, hyperuricemia

4. EMG

• abnormal at rest