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At a glance

One of the four glycogen storage diseases characterized by phosphofructokinase deficiency in the muscles and associated with abnormal deposition of glycogen in muscle tissues, exercise intolerance, and anemia. It is the least common type of glycogen storage disease.

Synonyms

Muscle Phosphofructokinase Deficiency; Tarui Disease; Glycogenosis Type VII.

History

Also named Tarui disease after the Japanese physician Seiichiro Tarui (born in 1927) who first described the disease in 1965.

Note of interest

It also affects animals, particularly dogs. Presentation of the canine form of the disease is similar to that of the human form. Most notably, PFK deficient dogs suffer from mild, but persistent, anemia with hemolytic episodes, exercise intolerance, hemoglobinuria, and pale or jaundiced mucous membranes. Muscle weakness and cramping are not uncommon but are not as frequent as they appear in human PFKM deficiency.

Incidence

Fewer than 50 cases reported (<10 for the infantile lethal form). This condition is mainly observed in the Ashkenazi Jewish people. Worldwide, the incidence is estimated at 1:1,000,000.

Classification

Human phosphofructokinase deficiency is categorized into four types: classic, late-onset, infantile, and hemolytic. These types are differentiated by age at which symptoms are observed. The description is as follows:

  • Classic Form: Classic phosphofructokinase deficiency is the most common type of this disorder. Characteristically, patients show exercise-induced muscle cramps and weakness (which might include rhabdomyolysis, myoglobinuria, as well as hemolytic anemia causing dark urine few hours after activity). Hyperuricemia is common, due to the kidneys’ inability to process uric acid following damage resulting from processing myoglobin. Nausea and vomiting following strenuous exercise is another common indicator. High level of bilirubin can be measured and jaundice observed. Symptoms usually appear in early childhood.

  • Late-Onset Form (Late-Onset PFK Deficiency): Clinical presentation that appears later in life. Common symptoms are myopathy, significant muscle weakness, and fatigue on light exercise. Most of the more severe symptoms observed with the classic type are absent in the late-onset form.

  • Infantile Form (Infantile Phosphofructokinase Deficiency Syndrome): Phosphofructokinase deficiency also presents in a rare infantile form. Infants display the Floppy Infant Syndrome (hypotonia), arthrogryposis, encephalopathy, and cardiomyopathy. Seizures can be observed in infants. Respiratory problems have been reported. Survival rate is low, and the cause of death is often associated to respiratory failure.

  • Hemolytic Form (Hemolytic Phosphofructokinase Deficiency Syndrome): The defining characteristic of this form is hemolytic anemia. Muscle weakness and pain are however not as common as observed in patients with the hemolytic PFK deficiency condition.

Genetic inheritance

Autosomal recessive; however, more males than females have been reported. The gene causing GSD VII (M subunit gene) has been mapped to chromosome 1.

Pathophysiology

Deficiency of muscle phosphofructokinase, which catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate in glycolysis. As a consequence, free or glycogen-derived glucose cannot be used as a source of energy ...

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