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Glycogen storage disease, type VII(GSD7)

MedGen UID:
5342
Concept ID:
C0017926
Disease or Syndrome
Synonyms: Glycogen storage disease type 7; GSD VII; GSD7; Muscle phosphofructokinase deficiency; Tarui disease
SNOMED CT: Glycogen storage disease, type VII (89597008); Muscle phosphofructokinase deficiency (89597008); Tarui's disease (89597008); GSD VII (89597008); Glycogen storage disease, type 7 (89597008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): PFKM (12q13.11)
 
Monarch Initiative: MONDO:0009295
OMIM®: 232800
Orphanet: ORPHA371

Definition

Glycogen storage disease VII is an autosomal recessive metabolic disorder characterized clinically by exercise intolerance, muscle cramping, exertional myopathy, and compensated hemolysis. Myoglobinuria may also occur. The deficiency of the muscle isoform of PFK results in a total and partial loss of muscle and red cell PFK activity, respectively. Raben and Sherman (1995) noted that not all patients with GSD VII seek medical care because in some cases it is a relatively mild disorder. [from OMIM]

Additional description

From MedlinePlus Genetics
Glycogen storage disease type VII (GSDVII) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in muscle cells. A lack of glycogen breakdown interferes with the function of muscle cells.

There are four types of GSDVII. They are differentiated by their signs and symptoms and the age at which symptoms first appear.

The classical form of GSDVII is the most common form. Its features usually appear in childhood. This form is characterized by muscle pain and cramps, often following moderate exercise; strenuous exercise can lead to nausea and vomiting. During exercise, muscle tissue can be abnormally broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can damage the kidneys and lead to kidney failure. Some people with the classical form of GSDVII develop high levels of a waste product called uric acid in the blood (hyperuricemia) because the damaged kidneys are unable to remove uric acid effectively. Affected individuals may also have elevated levels of a molecule called bilirubin in the blood that can cause yellowing of the skin and whites of the eyes (jaundice). Individuals with classical GSDVII often have elevated levels of an enzyme called creatine kinase in their blood. This finding is a common indicator of muscle disease.

Infants with the severe infantile form of GSDVII have low muscle tone (hypotonia) at birth, which leads to muscle weakness (myopathy) that worsens over time. Affected infants have a weakened and enlarged heart (cardiomyopathy) and difficulty breathing normally. Individuals with this form of GSDVII usually do not survive past their first year of life.

In the late-onset form of GSDVII, myopathy is typically the only feature. The muscle weakness appears in adulthood, although some individuals have difficulty with sustained exercise starting in childhood. The weakness generally affects the muscles closest to the center of the body (proximal muscles).

The hemolytic form of GSDVII is characterized by hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, causing a shortage of red blood cells (anemia). People with the hemolytic form of GSDVII do not experience any signs or symptoms of muscle pain or weakness related to the disorder.  https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-vii

Clinical features

From HPO
Myalgia
MedGen UID:
68541
Concept ID:
C0231528
Sign or Symptom
Pain in muscle.
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Exercise-induced myalgia
MedGen UID:
340638
Concept ID:
C1850830
Sign or Symptom
The occurrence of an unusually high amount of muscle pain following exercise.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
Exercise-induced myoglobinuria
MedGen UID:
337172
Concept ID:
C1845155
Finding
Presence of myoglobin in the urine following exercise.
Cholelithiasis
MedGen UID:
3039
Concept ID:
C0008350
Disease or Syndrome
Hard, pebble-like deposits that form within the gallbladder.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Reticulocytosis
MedGen UID:
60089
Concept ID:
C0206160
Finding
An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation.
Reduced erythrocyte 2,3-diphosphoglycerate concentration
MedGen UID:
868155
Concept ID:
C4022546
Finding
This term refers to an inappropriate low 2,3-DPG concentration in erythrocytes. 2,3-diphosphoglycerate (2,3-DPG) controls the movement of oxygen from red blood cells to tissues. Anemia is usually accompanied by an increased level of 2,3-DPG in order to promote tissue oxygenation.
Gout
MedGen UID:
42280
Concept ID:
C0018099
Disease or Syndrome
Recurrent attacks of acute inflammatory arthritis of a joint or set of joints caused by elevated levels of uric acid in the blood which crystallize and are deposited in joints, tendons, and surrounding tissues.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Increased variability in muscle fiber diameter
MedGen UID:
336019
Concept ID:
C1843700
Finding
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
Exercise-induced muscle cramps
MedGen UID:
383715
Concept ID:
C1855578
Finding
Sudden and involuntary contractions of one or more muscles brought on by physical exertion.
Exercise-induced muscle stiffness
MedGen UID:
343388
Concept ID:
C1855579
Finding
A type of muscle stiffness that occurs following physical exertion.
Exercise-induced muscle fatigue
MedGen UID:
340906
Concept ID:
C1855580
Finding
An abnormally increased tendency towards muscle fatigue induced by physical exercise.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Hyperuricemia
MedGen UID:
149260
Concept ID:
C0740394
Disease or Syndrome
An abnormally high level of uric acid in the blood.
Increased total bilirubin
MedGen UID:
152856
Concept ID:
C0741494
Finding
Increased concentration of total (conjugated and unconjugated) bilirubin in the blood.
Increased muscle glycogen content
MedGen UID:
409660
Concept ID:
C1968729
Finding
An increased amount of glycogen in muscle tissue.
Elevated circulating aldolase concentration
MedGen UID:
868464
Concept ID:
C4022858
Finding
Concentration of fructose 1,6-bisphosphate aldolase in the blood circulation above the upper limit of normal.
Increased circulating lactate dehydrogenase concentration
MedGen UID:
1377250
Concept ID:
C4477095
Finding
An elevated level of the enzyme lactate dehydrogenase in the blood circulation.
Reduced muscle 6-phosphofructokinase activity
MedGen UID:
1054705
Concept ID:
CN376955
Finding
Activity of the enzyme 6-phosphofructokinase in muscle tissue is below the lower limit of normal. 6-phosphofructokinase (EC 2.7.1.11) is also known as phosphofructokinase I and phosphohexokinase. The PFKM gene encodes the muscle isoform of phosphofructokinase. PFK catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate and is a key regulatory enzyme in glycolysis.

Recent clinical studies

Etiology

Reason SL, Godfrey RJ
Curr Opin Endocrinol Diabetes Obes 2020 Oct;27(5):283-290. doi: 10.1097/MED.0000000000000567. PMID: 32773572
Noury JB, Zagnoli F, Petit F, Marcorelles P, Rannou F
Sci Rep 2020 May 29;10(1):8765. doi: 10.1038/s41598-020-65770-y. PMID: 32472082Free PMC Article
Cenacchi G, Papa V, Costa R, Pegoraro V, Marozzo R, Fanin M, Angelini C
Virchows Arch 2019 Dec;475(6):671-686. Epub 2019 Jul 30 doi: 10.1007/s00428-019-02633-6. PMID: 31363843
Mineo I, Kono N, Shimizu T, Hara N, Yamada Y, Sumi S, Nonaka K, Tarui S
J Clin Invest 1985 Aug;76(2):556-60. doi: 10.1172/JCI112006. PMID: 3861621Free PMC Article
Vora S
Isozymes Curr Top Biol Med Res 1983;11:3-23. PMID: 6227585

Diagnosis

Cenacchi G, Papa V, Costa R, Pegoraro V, Marozzo R, Fanin M, Angelini C
Virchows Arch 2019 Dec;475(6):671-686. Epub 2019 Jul 30 doi: 10.1007/s00428-019-02633-6. PMID: 31363843
Tarnopolsky MA
Continuum (Minneap Minn) 2016 Dec;22(6, Muscle and Neuromuscular Junction Disorders):1829-1851. doi: 10.1212/CON.0000000000000403. PMID: 27922496
Toscano A, Musumeci O
Acta Myol 2007 Oct;26(2):105-7. PMID: 18421897Free PMC Article
Nakajima H, Raben N, Hamaguchi T, Yamasaki T
Curr Mol Med 2002 Mar;2(2):197-212. doi: 10.2174/1566524024605734. PMID: 11949936
Farmer PM
Ann Clin Lab Sci 1982 Nov-Dec;12(6):431-8. PMID: 6817693

Therapy

Haller RG, Vissing J
Neurology 2004 Jan 13;62(1):82-6. doi: 10.1212/wnl.62.1.82. PMID: 14718702
Ono A, Kuwajima M, Kono N, Mineo I, Nakagawa C, Tarui S, Matsuzawa Y
Neurology 1995 Jan;45(1):161-4. doi: 10.1212/wnl.45.1.161. PMID: 7824108
Vora S
Isozymes Curr Top Biol Med Res 1983;11:3-23. PMID: 6227585

Prognosis

Noury JB, Zagnoli F, Petit F, Marcorelles P, Rannou F
Sci Rep 2020 May 29;10(1):8765. doi: 10.1038/s41598-020-65770-y. PMID: 32472082Free PMC Article
Wu PL, Yang YN, Tey SL, Yang CH, Yang SN, Lin CS
Pediatr Int 2015 Aug;57(4):746-9. Epub 2015 Jun 25 doi: 10.1111/ped.12616. PMID: 26108272
Miró O, Laguno M, Masanés F, Perea M, Urbano-Márquez A, Grau JM
Semin Arthritis Rheum 2000 Jun;29(6):335-47. doi: 10.1053/sarh.2000.5753. PMID: 10924019
Nichols RC, Rudolphi O, Ek B, Exelbert R, Plotz PH, Raben N
Am J Hum Genet 1996 Jul;59(1):59-65. PMID: 8659544Free PMC Article
Moerman P, Lammens M, Fryns JP, Lemmens F, Lauweryns JM
Genet Couns 1995;6(1):15-20. PMID: 7794557

Clinical prediction guides

Noury JB, Zagnoli F, Petit F, Marcorelles P, Rannou F
Sci Rep 2020 May 29;10(1):8765. doi: 10.1038/s41598-020-65770-y. PMID: 32472082Free PMC Article
Miró O, Laguno M, Masanés F, Perea M, Urbano-Márquez A, Grau JM
Semin Arthritis Rheum 2000 Jun;29(6):335-47. doi: 10.1053/sarh.2000.5753. PMID: 10924019
Nichols RC, Rudolphi O, Ek B, Exelbert R, Plotz PH, Raben N
Am J Hum Genet 1996 Jul;59(1):59-65. PMID: 8659544Free PMC Article
Vora S
Isozymes Curr Top Biol Med Res 1983;11:3-23. PMID: 6227585
Cabello A, Benlloch T, Franch O, Feliú JF, Ricoy JR
Acta Neuropathol Suppl 1981;7:297-300. doi: 10.1007/978-3-642-81553-9_85. PMID: 6939256