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Genetic deficiencies of the glycogen phosphorylase system

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Abstract

Several types of glycogen storage disease attributable to a deficiency of phosphorylase or phosphorylase kinase have been described. These diseases have been divided according to clinical symptoms, mode of inheritance, and affected tissue. However, this classification is questionable, as the clinical symptoms of these different diseases are similar, the mode of inheritance is often difficult to establish, and the biochemical assays are subject to several technical problems. A better classification would be based upon the identification of mutations in the respective disease genes. The molecular heterogeneity, however, is large, and at least 10 genes are involved. Mutations have been found in the muscle phosphorylase gene in patients with muscle phosphorylase deficiency, in the gene encoding the liver a subunit of phosphorylase kinase in patients with X-linked liver glycogenosis, and in the gene for the muscle α subunit of phosphorylase kinase in a patient with muscle phosphorylase kinase deficiency. We review here the different deficiencies of the phosphorylase system.

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References

  • Barnard PJ, Derry JMJ, Ryder-Cook AS, Zander NF, Kilimann MW (1990) Mapping of the phosphorylase kinase alpha subunit gene on the mouse X chromosome. Cytogenet Cell Genet 53: 91–94

    Google Scholar 

  • Bender PK, Emerson CP (1987) Skeletal muscle phosphorylase kinase catalytic subunit mRNAs are expressed in heart tissue but not in liver. J Biol Chem 262: 8799–8805

    Google Scholar 

  • Berchtold MW, Egli R, Rhyner JA, Hameister H, Strehler EE (1993) Localization of the human bona fida calmodulin genes CALM 1, CALM 2 and CALM 3 to chromosomes 14q24–q31, 2p21.1–p21.3, and 19q13.2–q13.3. Genomics 16: 461–465

    Google Scholar 

  • Berg IET van den, Beurden EACM van, Malingré HEM, Amstel HKP van, Poll-The BT, Smeitink JAM, Lamers WH, Berger R (1995) X-linked liver phosphorylase kinase deficiency is associated with mutations in the human liver phosphorylase kinase a subunit. Am J Hum Genet 56: 381–387

    Google Scholar 

  • Billingsley GD, Cox DW, Duncan AM, Goodfellow PJ, Grzeschik KH (1994) Regional localization of loci on chromosome 14 using somatic cell hybrids. Cytogenet Cell Genet 66: 33–38

    Google Scholar 

  • Burke J, Hwang P, Anderson L, Gorin F, Fletterick R (1987) Intron/exon structure of the human gene for the muscle isozyme of glycogen phosphorylase. Proteins 2: 177–187

    Google Scholar 

  • Calalb MB, Fox, DT, Hanks SK (1992) Molecular cloning and enzymatic analysis of the rat homolog of “Phk-(T”, an isoform of phosphorylase kinase catalytic subunit. J Biol Chem 267: 1455–1463

    Google Scholar 

  • Clemens PR, Yamamoto M, Engel AG (1990) Adult phosphorylase b kinase deficiency. Ann Neurol 28: 529–530

    Google Scholar 

  • Davidson JJ, Ozcelik T, Hamacher C, Willems, PJ, Francke U, Kilimann MW (1992) cDNA encoding a liver isoform of the phosphorylase kinase α subunit: its structural gene maps to the locus of X-linked liver glycogenosis. Proc Natl Acad Sci USA 89:2096–2100

    Google Scholar 

  • DiMauro S, Bresolin N (1986) Phosphorylase deficiency. In: Engel AG, Banker BQ (eds) Myology. McGraw-Hill, New York, pp 1585–1601

    Google Scholar 

  • Fischer R, Koller M, Flura M, Mathews S, Strehler-Page M-A, Krebs J, Penniston JT, Carafoli E, Strehler EE (1988) Multiple divergent mRNAs code for a single human calmodulin. J Biol Chem 263:17055–17062

    Google Scholar 

  • Francke U, Darras BT, Zander NF, Kilimann MW (1989) Assignment of human genes for phosphorylase kinase subunits α (PHKA) to Xq12–q13 and β (PHKB) to 16q12–q13. Am J Hum Genet 45: 276–282

    Google Scholar 

  • Geng Y, Derry JMJ, Hendrickx J, Coucke P, Willems PJ, Barnard PJ (1993) Mapping of liver phosphorylase kinase α-subunit gene on the mouse X-chromosome. Genomics 15: 191–193

    Google Scholar 

  • Gray RGF, Kumar D, Whitfield AE (1983) Glycogen phosphorylase b kinase deficiency in three siblings. J Inherit Metab Dis 6: 107

    Google Scholar 

  • Guibaud P, Mathieu M (1972) Héterogénéité de la glycogénose type VI. Etude de l'activité de la phosphorylase leucocytaire dans deux familles. Arch Fr Pédiatr 29: 1043–1057

    Google Scholar 

  • Hanks SK (1989) Messenger ribonucleic acid encoding an apparent isoform of phosphorylase catalytic subunit is abundant in the adult testis. Mol Endocrinol 3: 110–116

    Google Scholar 

  • Harmann B, Zander NF, Kilimann MW (1991) Isoform diversity of phosphorylase kinase a and β subunits generated by alternative RNA splicing. J Biol Chem 266: 15631–15637

    Google Scholar 

  • Hendrickx J, Coucke P, Bossuyt P, Wauters J, Raeymaekers P, Marchau F, Smit GPA, Stolte I, Sardharwalla IB, Berthelot J, Bergh I van den, Berger R, Broeckhoven C van, Baussan C, Wapenaar M, Fernandes J, Willems PJ (1993) X-linked liver glycogenosis: localization and isolation of a candidate gene. Hum Mol Genet 2: 583–589

    Google Scholar 

  • Hendrickx J, Coucke P, Hors-Cayla MC, Smit GPA, Smeitink J, Berger R, Lee P, Shin YS, Deutsch J, Fernandes J, Willems PJ (1994) Localization of a new type of X-linked liver glycogenosis to the chromosomal region Xp22 containing the liver α-subunit of phosphorylase kinase (PHKA2). Genomics 21: 620–625

    Google Scholar 

  • Hendrickx J, Coucke P, Dams E, Lee P, Corbeel L, Odièvre M, Fernandes JF, Willems PJ (1995) Mutations in a phosphorylase kinase gene PHKA2 are responsible for X-linked liver glycogenosis. Hum Mol Genet 4: 77–83

    Google Scholar 

  • Hug G (1980) Pre- and postnatal diagnosis of glycogen storage disease. In: Burman D, Holton JB, Pennock CA (eds) Inherited disorders of carbohydrate metabolism. University Park Press, Baltimore, pp 327–368

    Google Scholar 

  • Hug G, Schubert WK (1970) Type VI glycogenosis: biochemical demonstration of liver phosphorylase deficiency. Biochem Biophys Res Commun 41: 1178–1184

    Google Scholar 

  • Hug G, Schubert WK, Chuck G (1966) Phosphorylase kinase of the liver: deficiency in a girl with increased hepatic glycogen. Science 153: 1534–1535

    Google Scholar 

  • Hug G, Schubert, WK, Chuck G (1969) Deficient activity of dephosphophosphorylase kinase and accumulation of glycogen in the liver. J Clin Invest 48: 704–715

    Google Scholar 

  • Huijing F, Fernandes J (1969) X-chromosomal inheritance of liver glycogenosis with phosphorylase kinase deficiency. Am J Hum Genet 21: 275–284

    Google Scholar 

  • Jones TA, Cruz e Silva EF da, Spurr NK, Sheer D, Cohen PTW (1990) Localization of the gene encoding the catalytic γ subunit of phosphorylase kinase to human chromosome bands 7pl2–q21. Biochem Biophys Acta 1048: 24–29

    Google Scholar 

  • Kilimann MW, Zander NF, Kuhn CC, Crabb JW, Meyer HE, Heilmeyer LMG (1988) The α and β subunits of phosphorylase kinase are homologous: cDNA cloning and primary structure of the β subunit. Proc Natl Acad Sci USA 85: 9381–9385

    Google Scholar 

  • Lafrenière RG, Brown CJ, Powers VE, Carrel I, Davies KE, Barker DF, Willard HF (1991) Physical mapping of 60 DNA markers in the Xp21.1–q21.3 region of the human X chromosome. Genomics 11: 352–363

    Google Scholar 

  • Lebo RV, Anderson LA, DiMauro S, Lynch E, Hwang P, Fletterick R (1990) Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence. Hum Genet 86: 17–24

    Google Scholar 

  • Lerner A, Iancu TC, Bashan N, Potashnik R, Moses S (1982) A new variant of glycogen storage disease type IXc. Am J Dis Child 136: 406–410

    Google Scholar 

  • Madlom M, Besley GTN, Cohen PTW, Martian VJ (1989) Phosphorylase b kinase deficiency in a boy with glycogenosis affecting both liver and muscle. Eur J Pediatr 149: 52–53

    Google Scholar 

  • Maire I, Baussan C, Moatti N, Mathieu M, Lemonnier A (1991) Biochemical diagnosis of hepatic glycogen storage disease: 20 years of French experience. Clin Biochem 24: 169–178

    Google Scholar 

  • Mizuta K, Hashimoto E, Tsmou A, Eishi Y, Takemura T, Narisawa K, Yamamura H (1984) A new type of glycogen storage disease caused by deficiency of cardiac phosphorylase kinase. Biochem Biophys Res Commun 119: 582–587

    Google Scholar 

  • Newgard CB, Nakano K, Hwang PK, Fletterick RJ (1986) Sequence analysis of the cDNA encoding human liver glycogen phosphorylase reveals tissue-specific codon usage (muscle/ G+C content). Proc Natl Acad Sci USA 83: 8132–8136

    Google Scholar 

  • Newgard CB, Littman DR, Genderen C van, Smith M, Fletterick RJ (1988) Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression and comparison with the human liver and muscle isozymes. J Biol Chem 263:3850–3857

    Google Scholar 

  • Ohtani Y, Matsuda I, Iwamasa T, Tamari H, Origuchi Y, Miike T (1982) Infantile glycogen storage myopathy in a girl with phosphorylase kinase deficiency. Neurology 32: 833–838

    Google Scholar 

  • Pickett-Gies CR, Walsh DA (1986) Phosphorylase kinase. In: Boyer PD, Krebs EG (eds) The enzymes. Academic Press, Orlando, pp 395–459

    Google Scholar 

  • Rao PN, Hayworth R, Akots G, Pettenati MJ, Bowden DW (1992) Physical localization of chromosome 20 markers using somatic cell hybrid cell lines and fluorescence in situ hybridization. Genomics 14: 532–535

    Google Scholar 

  • Schimke RN, Zakheim RM, Corder RC, Hug G (1973) Glycogen storage disease type IX: benign glycogenosis of liver and hepatic phosphorylase kinase deficiency. J Pediatr 83: 1031–1034

    Google Scholar 

  • SenGupta B, Friedberg F, Detera-Wadleigh SD (1987) Molecular analysis of human and rat calmodulin complementary DNA clones. Evidence for additional active genes in these species. J Biol Chem 262: 16663–16670

    Google Scholar 

  • Servidei S, Mitlay LA, Chodosh J, DiMauro S (1988) Fatal infantile cardiopathy caused by phosphorylase b kinase deficiency. J Pediatr 113: 82–85

    Google Scholar 

  • Tsujino S, Shanske S, DiMauro S (1993) Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease). N Engl J Med 329: 241–245

    Google Scholar 

  • Tsujino S, Shanske S, Nonaka I, Eto Y, Mendell JR, Fenichel GM, DiMauro S (1994a) Three new mutations in patients with myophosphorylase deficiency (McArdle disease). Am J Hum Genet 54: 44–52

    Google Scholar 

  • Tsujino S, Shanske S, Goto Y, Nonaka I, DiMauro S (1994b) Two mutations, one novel and one frequently observed, in Japanese patients with McArdle's disease. Hum Mol Genet 3: 1005–1006

    Google Scholar 

  • Tsujino S, Rubin LA, Shanske S, DiMauro S (1994c) An A-to-C substitution involving the translation initiation codon in a patient with myophosphorylase deficiency (McArdle's disease). Hum Mutat 4: 73–75

    Google Scholar 

  • Wauters J, Bossuyt P, Davidson J, Hendrickx J, Kilimann MW, Willems PJ (1992) Regional mapping of a liver (-subunit gene of phosphorylase kinase to the distal region of chromosome Xp. Cytogenet Cell Genet 60: 194–196

    Google Scholar 

  • Wawrzynczak EJ, Perham RN (1984) Isolation and nucleotide sequence of a cDNA encoding human calmodulin. Biochem Int 9:177–185

    Google Scholar 

  • Wehner M, Clemens PR, Engel AG, Kilimann MW (1994) Human muscle glycogenosis due to phosphorylase kinase deficiency associated with a nonsense mutation in the muscle isoform of the α subunit. Hum Mol Genet 3: 1983–1987

    Google Scholar 

  • Willems PJ, Gerver WJM, Berger R, Fernandes J (1990) The natural history of liver glycogenosis due to phosphorylase kinase deficiency: a longitudinal study of 41 patients. Eur J Pediatr 149:268–271

    Google Scholar 

  • Willems PJ, Hendrickx J, Auwera BJ van der, Vits L, Raeymaekers P, Coucke PJ, Bergh I van den, Berger R, Smit GPA, Broeckhoven C van, Kilimann MW, Elsen AF van, Fernandes JF (1991) Mapping of the gene for X-linked liver glycogenosis due to phosphorylase kinase deficiency to human chromosome region Xp22. Genomics 9: 565–569

    Google Scholar 

  • Zander NF, Meyer HE, Hoffmann-Posorske E, Crabb JW, Heilmeyer LMG, Kilimann MW (1988) CDNA cloning and complete primary structure of skeletal muscle phosphorylase kinase (α subunit). Proc Natl Acad Sci USA 85: 2929–2933

    Google Scholar 

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  1. Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium

    Jan Hendrickx & Patrick J. Willems

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  1. Jan Hendrickx
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  2. Patrick J. Willems
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Hendrickx, J., Willems, P.J. Genetic deficiencies of the glycogen phosphorylase system. Hum Genet 97, 551–556 (1996). https://doi.org/10.1007/BF02281858

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  • DOI: https://doi.org/10.1007/BF02281858

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