Genetics of Tarui Disease (Glycogen-Storage Disease Type VII or Phosphofructokinase Deficiency) Clinical Presentation

Updated: May 21, 2018
  • Author: Renee J Chosed, PhD; Chief Editor: Maria Descartes, MD  more...
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Presentation

History

The usual presenting symptoms of Tarui disease (glycogen-storage disease type VII) are exertional fatigue and muscle cramps. Most patients exhibit exertional fatigue in childhood and may experience nausea and vomiting, muscle cramps, hyperuricemia, myoglobinuria, or even anuria following high-intensity exercise. This constellation of signs and symptoms is characteristic not only of Tarui disease but a group of clinically and etiologically diverse conditions termed metabolic myopathies. The symptoms of exertional fatigue in patients with Tarui disease are typically more severe than those observed in McArdle disease (glycogen storage disease type V), the most common form of metabolic myopathy.

Hemolysis due to partial erythrocyte phosphofructokinase (PFK) deficiency may cause jaundice.

Myoglobinuria due to rhabdomyolysis has been reported. [7]

Hyperuricemia following exercise is due to accelerated degradation of muscle purine nucleotides, which serve as the substrates for the synthesis of uric acid. Manifestations of hyperuricemia may include arthritis.

Hypotonia, blindness, and psychomotor retardation may be the presenting symptoms of infantile-onset Tarui disease.

Cardiac dysfunction, arrhythmia, and anginal chest pain may be symptoms of late-onset Tarui disease. [16]

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Physical

See the list below:

  • Classic and late-onset
    • Muscle weakness, most pronounced following exercise
    • Fixed limb weakness
    • Muscle contractures
    • Jaundice
    • Joint pain
  • Fatal infantile variant
    • Hypotonia, muscle weakness
    • Cataracts
    • Joint contractures
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Causes

Tarui disease is genetic and is autosomal recessive.

Missense, [17, 18] splicing defects, [18, 19] , and frameshift mutations in the gene encoding the M subunit of PFK have been discovered in patients with Tarui disease. The M subunit gene, mapped to band 12p13, contains 24 exons and is approximately 30 kilobase (kb) in length.

Ashkenazi Jews share 2 common mutations in the PFKM gene. A splicing defect caused by the G-to-A base change at the first nucleotide in exon 5 accounts for 68% of mutant Ashkenazi alleles, and a deletion in exon 22 accounts for about 27% of mutant Ashkenazi alleles. [20]

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Complications

Renal failure may complicate myoglobinuria.

Gallstones may complicate hyperbilirubinemia.

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