Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Phosphofructokinase deficiency (glycogen storage disease VII, Tarui disease)

William J Craigen, MD, PhD
Basil T Darras, MD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


Glycogen is the stored form of glucose and serves as a buffer for glucose needs. It is composed of long polymers of a 1-4 linked glucose, interrupted by a 1-6 linked branch point every 4 to 10 residues. Glycogen is formed in periods of dietary carbohydrate loading and broken down when glucose demand is high or dietary availability is low (figure 1).

There are a number of inborn errors of glycogen metabolism that result from mutations in genes for virtually all of the proteins involved in glycogen synthesis, degradation, or regulation. Those disorders that result in abnormal storage of glycogen are known as glycogen storage diseases (GSDs). They have largely been categorized by number according to the chronology of recognition of the responsible enzyme defect (table 1). The age of onset varies from in utero to adulthood.

Glycogen is most abundant in liver and muscle, which are most affected by these disorders. The physiologic importance of a given enzyme in liver and muscle determines the clinical manifestations of the disease.

The main role of glycogen in the liver is to store glucose for release to tissues that are unable to synthesize significant amounts during fasting. The major manifestations of disorders of glycogen metabolism affecting the liver are hypoglycemia and hepatomegaly. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus".)

Glycogen is the primary source of energy for high-intensity muscle activity by providing substrates for the generation of adenosine triphosphate (ATP). The major manifestations of disorders of glycogen metabolism affecting muscle are muscle cramps, exercise intolerance and easy fatigability, and progressive weakness.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Aug 16, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Ronquist G, Rudolphi O, Engström I, Waldenström A. Familial phosphofructokinase deficiency is associated with a disturbed calcium homeostasis in erythrocytes. J Intern Med 2001; 249:85.
  2. Howard TD, Akots G, Bowden DW. Physical and genetic mapping of the muscle phosphofructokinase gene (PFKM): reassignment to human chromosome 12q. Genomics 1996; 34:122.
  3. Van Keuren M, Drabkin H, Hart I, et al. Regional assignment of human liver-type 6-phosphofructokinase to chromosome 21q22.3 by using somatic cell hybrids and a monoclonal anti-L antibody. Hum Genet 1986; 74:34.
  4. Vora S, Miranda AF, Hernandez E, Francke U. Regional assignment of the human gene for platelet-type phosphofructokinase (PFKP) to chromosome 10p: novel use of polyspecific rodent antisera to localize human enzyme genes. Hum Genet 1983; 63:374.
  5. DiMauro S, Miranda AF, Sakoda S, et al. Metabolic myopathies. Am J Med Genet 1986; 25:635.
  6. Raben N, Sherman JB. Mutations in muscle phosphofructokinase gene. Hum Mutat 1995; 6:1.
  7. Nichols RC, Rudolphi O, Ek B, et al. Glycogenosis type VII (Tarui disease) in a Swedish family: two novel mutations in muscle phosphofructokinase gene (PFK-M) resulting in intron retentions. Am J Hum Genet 1996; 59:59.
  8. Raben N, Sherman J, Miller F, et al. A 5' splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease). J Biol Chem 1993; 268:4963.
  9. Raben N, Sherman JB, Adams E, et al. Various classes of mutations in patients with phosphofructokinase deficiency (Tarui's disease). Muscle Nerve Suppl 1995; 3:S35.
  11. Layzer RB, Rowland LP, Ranney HM. Muscle phosphofructokinase deficiency. Arch Neurol 1967; 17:512.
  12. Haller RG, Lewis SF. Glucose-induced exertional fatigue in muscle phosphofructokinase deficiency. N Engl J Med 1991; 324:364.
  13. Haller RG, Vissing J. No spontaneous second wind in muscle phosphofructokinase deficiency. Neurology 2004; 62:82.
  14. Mineo I, Kono N, Hara N, et al. Myogenic hyperuricemia. A common pathophysiologic feature of glycogenosis types III, V, and VII. N Engl J Med 1987; 317:75.
  15. Mineo I, Tarui S. Myogenic hyperuricemia: what can we learn from metabolic myopathies? Muscle Nerve Suppl 1995; 3:S75.
  16. Danon MJ, Servidei S, DiMauro S, Vora S. Late-onset muscle phosphofructokinase deficiency. Neurology 1988; 38:956.
  17. Sivakumar K, Vasconcelos O, Goldfarb L, Dalakas MC. 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 1996; 46:1337.
  18. Malfatti E, Birouk N, Romero NB, et al. Juvenile-onset permanent weakness in muscle phosphofructokinase deficiency. J Neurol Sci 2012; 316:173.
  19. Amit R, Bashan N, Abarbanel JM, et al. Fatal familial infantile glycogen storage disease: multisystem phosphofructokinase deficiency. Muscle Nerve 1992; 15:455.
  20. Al-Hassnan ZN, Al Budhaim M, Al-Owain M, et al. Muscle phosphofructokinase deficiency with neonatal seizures and nonprogressive course. J Child Neurol 2007; 22:106.
  21. Swoboda KJ, Specht L, Jones HR, et al. Infantile phosphofructokinase deficiency with arthrogryposis: clinical benefit of a ketogenic diet. J Pediatr 1997; 131:932.
  22. Wu PL, Yang YN, Tey SL, et al. Infantile form of muscle phosphofructokinase deficiency in a premature neonate. Pediatr Int 2015; 57:746.
  23. Musumeci O, Bruno C, Mongini T, et al. Clinical features and new molecular findings in muscle phosphofructokinase deficiency (GSD type VII). Neuromuscul Disord 2012; 22:325.
  24. Bonilla E, Schotland DL. Histochemical diagnosis of muscle phosphofructokinase deficiency. Arch Neurol 1970; 22:8.
  25. Hays AP, Hallett M, Delfs J, et al. Muscle phosphofructokinase deficiency: abnormal polysaccharide in a case of late-onset myopathy. Neurology 1981; 31:1077.
  26. Akman HO, Oldfors A, DiMauro S. Glycogen storage diseases of muscle. In: Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach, Darras BT, Jones HRJ, Ryan MM, De Vivo DC. (Eds), Academic Press, San Diego 2015. p.735.