9. METABOLIC MYOPATHIES (Return to Disease group)
Disease phenotype
Item in this table
References
Gene symbol (chromosome)
protein
Glycogen storage disease Type II (Pompe) - (AR)
9.1
Hers HG. alpha-Glucosidase deficiency in generalized glycogenstorage disease (Pompe's disease). Biochem J. 1963 Jan;86:11-6. (13954110)
Martiniuk F, Bodkin M, Tzall S, Hirschhorn R. Identification of the base-pair substitution responsible for a human acid alpha glucosidase allele with lower "affinity" for glycogen (GAA 2) and transient gene expression in deficient cells. Am J Hum Genet 1990; 47: 440-445. (2203258)
Wokke, J. H. J.; Ausems, M. G. E. M.; van den Boogaard, M.-J. H.; Ippel, E. F.; van Diggelen, O.; Kroos, M. A.; Boer, M.; Jennekens, F. G. I.; Reuser, A. J. J.; Ploos van Amstel, H. K. : Genotype-phenotype correlation in adult-onset acid maltase deficiency. Ann. Neurol. 38: 450-454, 1995. (7668832)
GAA (17q25.2-q25.3)
Acid alpha-glucosidase preproprotein
Glycogen storage disease type IIIa - (AR)
9.2
Shen J, Bao Y, Chen YT. A nonsense mutation due to a single base insertion in the 3'-coding region of glycogen debranching enzyme gene associated with a severe phenotype in a patient with glycogen storage disease type IIIa. Hum Mutat. 1997;9(1):37-40. (8990006)
AGL (1p21)
Amylo-1,6-glucosidase, 4-alpha-glucanotransferase
Glycogen storage disease type IV - (AR)
9.3
Brown, B. I.; Brown, D. H. : Lack of an alpha-1,4-glucan: alpha-1,4-glucan 6-glycosyl transferase in a case of type IV glycogenosis. Proc. Nat. Acad. Sci. 56: 725-729, 1966. (15452297)
Bao, Y.; Kishnani, P.; Wu, J.-Y.; Chen, Y.-T. : Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene. J. Clin. Invest. 97: 941-948, 1996. (5229990)
Bruno C, van Diggelen OP, Cassandrini D, Gimpelev M, Giuffrè B, Donati MA, Introvini P, Alegria A, Assereto S, Morandi L, Mora M, Tonoli E, Mascelli S, Traverso M, Pasquini E, Bado M, Vilarinho L, van Noort G, Mosca F, DiMauro S, Zara F, Minetti C. Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV). Neurology. 2004 Sep 28;63(6):1053-8. (8613547)
GBE1 (3p12)
Glucan (1,4-alpha-), branching enzyme 1 (glycogen branching enzyme, Andersen disease, glycogen storage disease type IV)
Glycogen storage disease Type V (McArdle) - (AR)
9.4
Schmid, R.; Mahler, R. : Chronic progressive myopathy with myoglobinuria: demonstration of a glycogenolytic defect in the muscle. J. Clin. Invest. 38: 2044-2058, 1959. (6587566)
Lebo RV, Gorin F, Fletterick RJ, Kao FT, Cheung MC, Bruce BD, Kan YW. High-resolution chromosome sorting and DNA spot-blot analysis assign McArdle's syndrome to chromosome 11. Science. 1984 Jul 6;225(4657):57-9. (14442994)
Tsujino S, Shanske S, DiMauro S. Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease). N Engl J Med. 1993 Jul 22;329(4):241-5. (8316268)
PYGM (11q12-q13.2)
Glycogen phosphorylase
Glycogen storage disease Type VII (Tarui) - (AR)
9.5
Tarui, S.; Okuno, G.; Ikura, Y.; Tanaka, T.; Suda, M.; Nishikawa, M. : Phosphofructokinase deficiency in skeletal muscle: a new type of glycogenosis. Biochem. Biophys. Res. Commun. 19: 517-523, 1965. (6213050)
Vora S, Durham S, de Martinville B, George DL, Francke U. Assignment of the human gene for muscle-type phosphofructokinase (PFKM) to chromosome 1 (region cen leads to q32) using somatic cell hybrids and monoclonal anti-M antibody. Somatic Cell Genet. 1982 Jan;8(1):95-104. (14339001)
PFKM (12q13.3)
Phosphofructokinase, muscle
Glycogen storage disease type IXd (ex type VIII) or muscle phosphorylase kinase defiency - (XR)
9.6
Wehner M, Clemens PR, Engel AG, Kilimann MW. Human muscle glycogenosis due to phosphorylase kinase deficiency associated with a nonsense mutation in the muscle isoform of the alpha subunit. Hum Mol Genet. 1994 Nov;3(11):1983-7. (7874115)
PHKA1 (Xq13)
Phosphorylase b kinase, alpha submit
Glycogenosis type XIV - (AR)
9.7
Stojkovic, T., Vissing, J., Petit, F., Piraud, M., Orngreen, M. C., Andersen, G., Claeys, K. G., Wary, C., Hogrel, J.-Y., Laforet, P. Muscle glycogenosis due to phosphoglucomutase 1 deficiency. New Eng. J. Med. 361: 425-427, 2009. (19625727)
PGM1 (1p31)
Phosphoglucomutase 1
Glycogenosis type XV - (AR)
9.8
Moslemi, A.-R., Lindberg, C., Nilsson, J., Tajsharghi, H., Andersson, B., Oldfors, A. Glycogenin-1 deficiency and inactivated priming of glycogen synthesis. New Eng. J. Med. 362: 1203-1210, 2010. (25272951)
Malfatti E, Nilsson J, Hedberg-Oldfors C, Hernandez-Lain A, Michel F, Dominguez-Gonzalez C, Viennet G, Akman HO, Kornblum C, Van den Bergh P, Romero NB, Engel AG, DiMauro S, Oldfors A. A new muscle glycogen storage disease associated with glycogenin-1 deficiency. Ann Neurol. 2014 Oct 1. doi: 10.1002/ana.24284. (20357282)
GYG1 (3q24)
Glycogenin 1
Glycogen storage disease type 0 - (AR)
9.9
Kollberg G, Tulinius M, Gilljam T, Östman-Smith I, Forsander G, Jotorp P, Oldfors A, Holme E. Cardiomyopathy and exercise intolerance in muscle glycogen storage disease 0. N Engl J Med. 2007 Oct 11;357(15):1507-14. (17928598)
GYS1 (19q13.3)
Glycogen synthase 3 glycogen synthase 1 (muscle) glycogen synthase 1 (muscle)
Glycogen storage disease of heart, lethal congenital - (AD)
9.10
Burwinkel, B., Scott, J. W., Buhrer, C., van Landeghem, F. K. H., Cox, G. F., Wilson, C. J., Hardie, D. G., Kilimann, M. W. Fatal congenital heart glycogenosis caused by a recurrent activating R531Q mutation in the gamma-2-subunit of AMP-activated protein kinase (PRKAG2), not by phosphorylase kinase deficiency. Am. J. Hum. Genet. 76: 1034-1049, 2005. (15877279)
PRKAG2 (7q31)
Protein kinase, AMP-activated, gamma 2 non-catalytic subunit
Polyglucosan storage myopathy - (AR)
9.11
Nilsson J, Schoser B, Laforet P, et al. Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1. Ann Neurol. 2013 Jun 24 (23798481)
RBCK1 (20p13)
RanBP-type and C3HC4-type zinc finger containing 1 (heme-oxidized IRP2 ubiquitin ligase 1)
Phosphoglycerate kinase deficiency - (XR)
9.12
Rosa R, George C, Fardeau M, Calvin MC, Rapin M, Rosa J. A new case of phosphoglycerate kinase deficiency: PGK Creteil associated with rhabdomyolysis and lacking hemolytic anemia. Blood. 1982 Jul;60(1):84-91. (7082849)
DiMauro S, Dalakas M, Miranda AF. Phosphoglycerate kinase deficiency: another cause of recurrent myoglobinuria. Ann Neurol. 1983 Jan;13(1):11-9. (6830158)
PGK1 (Xq13)
Phosphoglycerate kinase 1
Phosphoglycerate mutase deficiency - (AR)
9.13
DiMauro S, Dalakas M, Miranda AF. Phosphoglycerate kinase deficiency: another cause of recurrent myoglobinuria. Ann Neurol. 1983 Jan;13(1):11-9. (6830158)
Edwards YH, Sakoda S, Schon E, Povey S. The gene for human muscle-specific phosphoglycerate mutase, PGAM2, mapped to chromosome 7 by polymerase chain reaction. Genomics. 1989 Nov;5(4):948-51. (2556344)
Castella-Escola J, Mattei MG, Ojcius DM, Passage E, Valentin C, Cohen-Solal M. Related Articles, Links In situ mapping of the muscle-specific form of phosphoglycerate mutase gene to human chromosome 7p12-7p13. Hum Genet. 1990 Jan;84(2):210-2. (2153628)
Tsujino S, Shanske S, Sakoda S, Fenichel G, DiMauro S. The molecular genetic basis of muscle phosphoglycerate mutase (PGAM) deficiency. Am J Hum Genet. 1993 Mar;52(3):472-7. (8447317)
PGAM2 (7p13-p12)
Phosphoglycerate mutase 2 (muscle)
Lactate dehydrogenase-A deficiency - (AR)
9.14
Kanno T, Sudo K, Takeuchi I, Kanda S, Honda N, Nishimura Y, Oyama K. Bivariate ratio monitoring in clinical laboratories. Am J Clin Pathol. 1981 Dec;76(6):782-7. (7315796)
Scrable HJ, Johnson DK, Rinchik EM, Cavenee WK. Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2182-6. (2315312)
LDHA (11p15.4)
Lactate dehydrogenase A
Enolase deficiency - (AD)
9.15
Comi, G. P.; Fortunato, F.; Lucchiari, S.; Bordoni, A.; Prelle, A.; Jann, S.; Keller, A.; Ciscato, P.; Galbiati, S.; Chiveri, L.; Torrente, Y.; Scarlato, G.; Bresolin, N. : Beta-enolase deficiency, a new metabolic myopathy of distal glycolysis. Ann. Neurol. 50: 202-207, 2001. (11506403)
ENO3 (17pter-p11)
Enolase 3, beta muscle specific
Carnitine palmitoyl-transferase deficiency - (AR)
9.16
DiMauro S, DiMauro PM. Muscle carnitine palmityltransferase deficiency and myoglobinuria. Science. 1973 Nov 20;182(115):929-31. (4745596)
Finocchiaro G, Taroni F, Rocchi M, Martin AL, Colombo I, Tarelli GT, DiDonato S. cDNA cloning, sequence analysis, and chromosomal localization of the gene for human carnitine palmitoyltransferase. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):661-5. Erratum in: Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10981. (1988962)
Taroni F, Verderio E, Dworzak F, Willems PJ, Cavadini P, DiDonato S. Identification of a common mutation in the carnitine palmitoyltransferase II gene in familial recurrent myoglobinuria patients. Nat Genet. 1993 Jul;4(3):314-20. (8358442)
CPT2 (1p32)
Carnitine palmitoyltransferase II
Primary systemic carnitine deficiency - (AR)
9.17
Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, Nikaido H, Sai Y, Koizumi A, Shoji Y, Takada G, Matsuishi T, Yoshino M, Kato H, Ohura T, Tsujimoto G, Hayakawa J, Shimane M, Tsuji A. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet. 1999 Jan;21(1):91-4. (9916797)
SLC22A5 (5q31)
Solute carrier family 22 member 5
Carnitine acylcarnitine translocase deficiency - (AR)
9.18
Huizing, M.; Iacobazzi, V.; IJlst, L.; Savelkoul, P.; Ruitenbeek, W.; van den Heuvel, L.; Indiveri, C.; Smeitink, J.; Trijbels, F; Wanders, R.; Palmieri, F. : Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient. Am. J. Hum. Genet. 61: 1239-1245, 1997. (10697964)
Ogawa, A.; Yamamoto, S.; Kanazawa, M.; Takayanagi, M.; Hasegawa, S.; Kohno, Y. : Identification of two novel mutations of the carnitine/acylcarnitine translocase (CACT) gene in a patient with CACT deficiency. J. Hum. Genet. 45: 52-55, 2000. (9399886)
SLC25A20 (3p21.31)
Carnitine-acylcarnitine translocase
Multiple acyl-CoA dehydrogenase deficiency (MADD; Glutaric aciduria type IIA - (AR)
9.19
Indo, Y.; Glassberg, R.; Yokota, I.; Tanaka, K. : Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II--and identification of glycine substitution for valine-157 in the sequence of the precursor, producing an unstable mature protein in a patient. Am. J. Hum. Genet. 49: 575-580, 1991. (1430199)
Freneaux, E.; Sheffield, V. C.; Molin, L.; Shires, A.; Rhead, W. J. : Glutaric acidemia type II: heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha-subunit of electron transfer flavoprotein in eight patients. J. Clin. Invest. 90: 1679-1686, 1992. (1882842)
ETFA (15q23-q25)
Electron-transfer-flavoprotein, alpha polypeptide
Multiple acyl-CoA dehydrogenase deficiency (MADD; Glutaric aciduria type IIB) - (AR)
9.20
Colombo, I.; Finocchiaro, G.; Garavaglia, B.; Garbuglio, N.; Yamaguchi, S.; Frerman, F. E.; Berra, B.; DiDonato, S. : Mutations and polymorphisms of the gene encoding the beta-subunit of the electron transfer flavoprotein in three patients with glutaricacidemia type II. Hum. Molec. Genet. 3: 429-435, 1994. (7912128)
ETFB (19q13.3-q13.4)
Electron-transfer-flavoprotein, beta polypeptide
Multiple acyl-CoA dehydrogenase deficiency (MADD; Glutaric aciduria type IIC) - (AR)
9.21
Olsen, R. K. J.; Andresen, B. S.; Christensen, E.; Bross, P.; Skovby, F.; Gregersen, N. : Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum. Mutat. 22: 12-23, 2003. (12815589)
ETFDH (4q32-q35)
Electron-transferring-flavoprotein dehydrogenase
Acyl-CoA dehydrogenase (very long chain) deficiency (VLCAD deficiency) - (AR)
9.22
Aoyama, T.; Uchida, Y.; Kelley, R. I.; Marble, M.; Hofman, K.; Tonsgard, J. H.; Rhead, W. J.; Hashimoto, T. : A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase. Biochem. Biophys. Res. Commun. 191: 1369-1372, 1993. (10077518)
Aoyama, T.; Souri, M.; Ueno, I.; Kamijo, T.; Yamaguchi, S.; Rhead, W. J.; Tanaka, K.; Hashimoto, T. : Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients. Am. J. Hum. Genet. 57: 273-283, 1995. (7479827)
Strauss, A. W.; Powell, C. K.; Hale, D. E.; Anderson, M. M.; Ahuja, A.; Brackett, J. C.; Sims, H. F. : Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood. Proc. Nat. Acad. Sci. 92: 10496-10500, 1995. (7668252)
Mathur, A.; Sims, H. F.; Gopalakrishnan, D.; Gibson, B.; Rinaldo, P.; Vockley, J.; Hug, G.; Strauss, A. W. : Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death. Circulation 99: 1337-1343, 1999. (8466512)
ACADVL (17p13)
Acyl-Coenzyme A dehydrogenase, very long chain
ACAD9-deficient mild myopathy - (AR)
9.23
Fragaki K., Chaussenot A., Boutron A., et al. Severe defect in mitochondrial complex I assembly with mtDNA deletions in ACAD9-deficient mild myopathy. Muscle Nerve 2016; doi:10.1002/mus.25262 (27438479)
ACAD9 (3q21.3)
acyl-CoA dehydrogenase family member 9
Triglyceride storage disease with impaired long-chain fatty acid oxidation (Chanarin-Dorfman syndrome) - (AR)
9.24
Lefevre, C.; Jobard, F.; Caux, F.; Bouadjar, B.; Karaduman, A.; Heilig, R.; Lakhdar, H.; Wollenberg, A.; Verret, J.-L.; Weissenbach, J.; Ozguc, M.; Lathrop, M.; Prud'homme, J.-F.; Fischer, J. : Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. Am. J. Hum. Genet. 69: 1002-1012, 2001. (11590543)
ABHD5 (3p25.3-p24.3)
Abhydrolase domain containing 5
Neutral lipid storage disease with myopathy without ichthyosis - (AR)
9.25
Fischer J, Lefevre C, Morava E, Mussini J M, Laforet P, Negre-Salvayre A, Lathrop M, Salvayre R. The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nat Genet 2007; 39: 28-30. (17187067)
PNPLA2 (1p15.5)
Adipose triglyceride lipase (desnutrin)
Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (Lipid storage myopathy) - (AR)
9.26
Olsen RK, Olpin SE, Andresen BS, Miedzybrodzka ZH, Pourfarzam M, Merinero B, Frerman FE, Beresford MW, Dean JC, Cornelius N, Andersen O, Oldfors A, Holme E, Gregersen N, Turnbull DM, Morris AA. ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain 2007;130:2045-2054 (17584774)
ETFDH (4q32-q35)
Electron-transferring-flavoprotein dehydrogenase
Reccurrent myoglobinuria, autosomal recessive - (AR)
9.27
Zeharia, A., Shaag, A., Houtkooper, R. H., Hindi, T., de Lonlay, P., Erez, G., Hubert, L., Saada, A., de Keyzer, Y., Eshel, G., Vaz, F. M., Pines, O., Elpeleg, O. Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood. Am. J. Hum. Genet. 83: 489-494, 2008. Note: Erratum: Am. J. Hum. Genet. 84: 95 only, 2009. (18817903)
LPIN1 (2p25.1)
Lipin 1 (phosphatidic acid phosphatase 1)
Infantile neuroaxonal dystrophy and neutral lipid storage disease with myopathy - (AR)
9.28
Saunders CJ1, Moon SH, Liu X, Thiffault I, Coffman K, LePichon JB, Taboada E, Smith LD, Farrow EG, Miller N, Gibson M, Patterson M, Kingsmore SF, Gross RW. Loss of function variants in human PNPLA8 encoding calcium-independent phospholipase A2 ? recapitulate the mitochondriopathy of the homologous null mouse. Hum Mutat. 2015 Mar;36(3):301-6. doi: 10.1002/humu.22743. (25512002)
PNPLA8 (7q31.1)
Patatin-like phospholipase domain containing 8