6-phosphofructokinase deficiency

HI. Hamaguchi, T Nakajima, H., Noguchi, T., Ono, A., Kono, N., Tarui, S., Kuwajima, M., and Matsuzawa, Y., A new variant of muscle phosphofructokinase deficiency in a Japanese case with abnormal splicing. Biochem. Biophys. Res. Commun. 202,444-449 (1994). 

N2. Nakajima, H., Kono, N Yamasaki, T Hotta, K., Kawachi, M Kuwajima, M., Noguchi, T., Tanaka, T., and Tarui, S Genetic defect in muscle phosphofructokinase deficiency Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5 -splice site. J. Biol. Chem. 265, 9392-9395 (1990). 

Rl. Raben, N., Sherman, J., Miller, E, Mena, H., and Plotz, P., A5 splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease). J. Biol. Chem. 268,4963-4967 (1993). 

R2. Raben, N., Exelbert, R., Spiegel, R., Sherman, J. B Nakajima, H., Plotz, P., and Heinisch, J., Functional expression of human mutant phosphofructokinase in yeast Genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency. Am. J. Hum. Genet. 56, 131-141 (1995). 

T14. Tarui, S., Okuno, G., Ikuno, Y Tanaka, T Suda, M and Nishikawa, M., Phosphofructokinase deficiency in skeletal muscle. A new type of glycogenesis. Biochem. Biophys. Res. Commun. 19,517-523(1965). 

T23. Tsujino, S Servidei, S Tonin, P., Shanske, S., Azan, G., and DiMauro, S., Identification of three novel mutations in non-Ashkenazi Italian patients with muscle phosphofructokinase deficiency. Am. J. Hum. Genet. 54,812-819 (1994). 

Vora S, Corash L, Engel WK, Durham S, Seaman C, Piomelli S (1980) The molecular mechanism of the inherited phosphofructokinase deficiency associated with hemolysis and myopathy. Blood 55 629-635... 

Chance, B., Eleff, S., Bank, W Leigh, J.S., Wamell, R. (1982). 3IP NMR studies of control of mitochondrial function in phosphofructokinase-deficient human skeletal muscle. Proc. Natl. Acad. Sci. USA 79, 7714-7718. 

Phosphofructokinase deficiency (Tarui s disease) is an inborn error of glycogen metabolism characterised by a phosphofructokinase deficiency in the muscles, and associated with abnormal deposition of glycogen in muscle tissues, occasionally with myoglobinuria. The symptoms are similar to those seen in McArdle s disease. Classic Tarui s disease typically presents in childhood with exercise intolerance and anaemia. The fatal infantile variant presents in the first year of life. All reported patients have died by age four years. A late-onset variant manifests itself during later adulthood with progressive limb weakness without myoglobinuria or cramps. It is an autosomal recessive inheritance. Males are slightly more often affected than females. 

Phosphofructokinase deficiency (OMIM 171850) is a rare autosomal recessively inherited disorder. Since red cells contain both M and L submits, mutations affecting the genes coding for these subunits wfil affect enzyme activity. Thus when the PFK deficiency mutation affects only the L subunit, RBCs have only M4 and are PFK deficient. In such cases, there is a mild hemolytic disorder without myopathy. However, when the M subunit is deficient, muscle PFK is virtually absent together with partial PFK deficiency in RBCs, which wfil have only L. Therefore deficiency of the M subunit causes myopathy and a mild hemolytic disorder. 

Fujii H, Miwa S. Other erythrocyte enzyme deficiencies associated with non-haematological symptoms phosphoglycerate kinase and phosphofructokinase deficiency. Baillieres Best Pract Res Clin Haematol 2000 13 141-8. 

Some enzymopathies of erythrocytes may be associated with multisystem disease (e.g., aldolase deficiency with mental and growth retardation). Individuals with 6-phosphofructokinase deficiency exhibit hemolysis and myopathy and have increased deposition of muscle glycogen (a glycogen storage disease see Chapter 15). The myopathy is usually characterized by muscle weakness and exercise intolerance. (See also Chapters 10, 15, and 28.)... 

GSD type VII, Tarui sdisease Muscle phosphofructokinase deficiency causes pronounced decrease in exercise tolerance. 

Table 15.14. Glycogen storage disease type 7 (muscle phosphofructokinase deficiency) ...

Fig. 12. Phosphorus-31 spectra and muscle pH values obtained from forearm muscles of a patient with phosphofructokinase deficiency. Peak assignments a, SP b, Pj c, PCr, d, e, f, y-, a-, and phosphates of ATP, respectively. From Edwards et al. (1982).

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