Glycogen storage disease type V
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]
Glycogen storage disease type V | |
ICD-10 | E74.0 |
---|---|
ICD-9 | 271.0 |
OMIM | 232600 |
DiseasesDB | 5307 |
eMedicine | med/911 |
MeSH | D006012 |
Overview
Glycogen storage disease type V also known as McArdle's disease is caused by the deficiency of myophosphorylase. In 1951, Brian McArdle first described glycogen storage type V disease. It is an autosomal recessive disorder caused by mutation of the gene PYGM which is located on chromosome 11q13. Myophosphorylase is the isozyme of phosphorylase specific to muscles. Its deficiency leads to blockage of carbohydrate metabolic pathways causing accumulation of excess glycogen in the muscles. Muscles are unable to produce energy from glycogen and may lead to rhabdomyolysis. Glycogen storage disease type V commonly affects individuals in the 2nd-3rd decade of their life. There is insufficient evidence to recommend routine screening for glycogen storage disease type V but carrier screening of at-risk relatives may be done. Different individuals present uniquely depending on the severity on enzyme activity. Some adults can develop progressive proximal weakness or fixed motor weakness. A "Second-wind phenomenon" can be seen in patients suffering from glycogen storage disease type V. Burgundy-colored urine can be seen after an intense session of exercise due to rhabdomyolysis. On physical examination persistent weakness and muscle wasting may be seen as the patient ages. Laboratory findings may show elevated levels of creatine kinase levels in almost 90% of patients suffering from glycogen storage disease type V. Forearm exercise test and electromyography are used to diagnose GSD type V. Treatment includes dietary modification and mild to moderate aerobic exercises like walking or bicycling.
Historical Perspective
- Glycogen storage disease type V was first described by Brian McArdle, a Scottish physician, in 1951.[1]
- In 1993, the first PYGM pathogenic mutations were described.[2]
Classification
There is no established system for the classification of glycogen storage disease type V.
Pathophysiology
- Glycogen storage disease type V is caused by the deficiency of liver myophosphorylase.
- Normal function of phophorylase is [3]
- Maintains the glucose homeostasis.
- Leads to the degradation of glycogen into glucose-1-phosphate.
- Alpha-1,4-glucoside residues are removed from the outer branches of the glycogen molecule.
- Degradation is done until glycogen is broken down to branches of approximately 4 glucosyl units.
- 3 isozymes of phosphorylase are found in the muscles, liver, and brain.
- Myophosphorylase is the isozyme specific to muscles.
- Carbohydrate metabolic pathways are blocked which lead to accumulation of excess glycogen in muscles.
- Muscles are unable to produce energy from glycogen due to deficiency of this enzyme.
- There is an increase in the cellular mechanical stress due to:
- Accumulation of glycogen.
- Downregulation of sodium-potassium pumps.
- Elevation of sarcoplasmic calcium.
- This processes may lead to rhabdomyolysis.[4]
- Muscle damage is done due to oxidative stress and purine nucleotide metabolism.
- Hypoglycemia is not seen as liver phosphorylase is not involved.
Causes
- Glycogen storage disease type V is an autosomal recessive disorder.
- Glycogen storage disease type V is caused by the deficiency of the myophosphorylase enzyme. PYGM gene mutation responsible for the myophosphorylase enzyme deficiency is located on chromosome 11q13.[5]
- Disease severity can be correlated with the genotype at the angiotensin-converting enzyme (ACE) locus.
Differentiating Glycogen storage disease type V from Other Diseases
Glycogen storage disease | Enzyme deficiency | Genetics | History and symptoms | Physical examination | Laboratory findings | Imaging | Other features | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene mutation | Inheritance | Chromosome | Hypoglycemia | Muscle weakness | Hypotonia | Hepatomegaly | Elevated CK | Cardiomegaly | |||||
Glycogen storage disease type I | Von Gierke's disease | GSD type Ia | Glucose-6-phosphatase | G6PC gene mutation | Autosomal recessive | 17q21 | + | + | + | + | - | - |
|
GSD type Ib | Microsomal glucose-6-phosphate transporter | SLC37A4 gene mutation | Autosomal recessive | 11q23 | |||||||||
Glycogen storage disease type II | Pompe disease | Infantile onset | Alpha acid-glucosidase | GAA gene | Autosomal recessive | 17q25 | - | + | + | + | + | + |
|
Late onset | Autosomal recessive | - | + | + | + | + | +/- | ||||||
Glycogen storage disease type III | Cori disease | GSD type IIIa | Debranching enzyme (deficiency in muscle and liver) | AGL gene mutation | Autosomal recessive | 1p21 | + | + | - | + | + | + |
|
GSD type IIIb | Debranching enzyme (deficiency in liver only) | Autosomal recessive | |||||||||||
Glycogen storage disease type IV | Andersen's disease | Branching enzyme | GBE1 gene mutation | Autosomal recessive | 3p12 | + | + | - | + | + | + | - | |
Glycogen storage disease type V | McArdle disease | Muscle glycogen phosphorylase | PYGM gene mutation | Autosomal recessive | 11q13 | - | + | - | - | + | - |
| |
Glycogen storage disease type VI | Hers' disease | Autosomal | Liver glycogen phosphorylase | PYGL gene mutation | Autosomal recessive | 14q22 | +/- | + | +/- | + | - | - |
|
X-linked | X-linked recessive | ||||||||||||
Glycogen storage disease type VII | Tauri's disease | Muscle phosphofruktokinase | PFKM gene mutation | Autosomal recessive | 12q13 | + | + | - | - | + | + | ||
Glycogen storage disease type IX | GSD type IXa | Phosphorylase b kinase (deficiency in liver only) | PHKA2 gene mutation | X-linked recessive | Xp22 | + | - | - | + | - | - |
| |
GSD type IXb | Phosphorylase b kinase (deficiency in liver and muscle) | PHKB gene mutation | Autosomal recessive | 16q12 | + | - | - | + | - | - |
| ||
Glycogen storage disease type X | Phosphoglycerate mutase | PGAM2 gene mutation | Autosomal recessive | 7p13 | - | - | - | - | + | - |
| ||
Glycogen storage disease type XI | Lactate dehydrogenase A deficiency | LDH A deficiency | LDHA gene mutation | Autosomal recessive | 11p15 | - | - | - | - | + | - |
| |
Glycogen storage disease type XII | Aldolase A deficiency | Aldolase A | ALDOA gene mutation | Autosomal recessive | 16p11 | - | + | - | + | - | - |
| |
Glycogen storage disease type XIII | Beta-enolase | ENO3 gene mutation | Autosomal recessive | 17p13 | - | + | - | - | + | - | - | ||
Glycogen storage disease type XIV | Phosphoglucomutase type 2 | PGM1 gene mutation | Autosomal recessive | 1p31 | +/- | + | - | - | + | - |
| ||
Glycogen storage disease type 0 | Lewis' disease | Hepatic glycogen synthase | GYS1 gene mutation (muscle)
GYS2 gene mutation (liver) |
Autosomal recessive | 12p12 | + | - | - | - | - | - |
|
Epidemiology and Demographics
- The prevalence of glycogen storage disease type V is approximately 0.6 in 100,000 individuals in spanish community.[6]
- The prevalence of glycogen storage disease type V is approximately 1 in 100,000 individuals in Texas, USA.[7]
- Glycogen storage disease type V commonly affects individuals in the 2nd-3rd decade of life.
Risk Factors
- The most potent risk factor in the development of glycogen storage disease type V is a sibling with glycogen storage disease type V.
Screening
- There is insufficient evidence to recommend routine screening for glycogen storage disease type V.
Natural History, Complications, and Prognosis
Complications
- Glycogen storage disease type V may have potential anesthetic and perioperative risks.[8]
- Statin should be used with caution as they can lead to myopathy in individuals suffering from glycogen storage disease type V.
Prognosis
- Glycogen storage disease type V is a chronic disorder.
Diagnosis
Diagnostic Study of Choice
Forearm exercise test
- Forearm exercise test is of 2 types:
- Normal chemical reactions and products of muscle activity are analysed.
- One-second handgrips are performed every other second for one minute (approximately 30 contractions)
- Blood samples are taken to check for lactate, ammonia, and creatine kinase before starting the test and at 1, 2, 4, 6, 10, 20, and 30 minutes after the end of the exercise.
- A flat venous lactate curve with normal increase in ammonia is diagnostic of myophosphorylase deficiency.
- Earlier blood pressure cuff was used instead of handgrips, but it was stopped because it lead to more muscle pain and acute compartment syndrome.
Electromyography
- Electromyography of resting muscle are normal.
- No electrical activity during contracture is diagnostic of myophosphorylase deficiency.
History and Symptoms
- Different individuals present uniquely depending on the severity on enzyme deficiency.
- Some adults can develop:
- Progressive proximal weakness.
- Fixed motor weakness.
- Second-wind phenomenon:[11]
- When a patient nearing fatigue slows down the intensity of exercise to a certain level, it can be increased again without recurrence of symptoms.[12]
- This phenomenon may be due to recruitment of: [13]
- Increased number of motor units
- Increased cardiac output
- Use of free fatty acids for muscle metabolism
- Burgundy-colored urine can be seen after an intense session of exercise.
- This is believed to be due to rhabdomyolysis.
Physical Examination
- Normal muscle strength and reflexes may be seen.
- Persistent weakness and muscle wasting may be seen as the patient ages.
Laboratory Findings
- Creatine kinase levels are checked in all cases with suspicion of glycogen storage disease.
- 90% patients suffering from glycogen storage disease type V have elevated levels.
- Fasting glucose testing is done to rule out hypoglycemia.
- Myoglobinuria
- Urine analysis is done to check for it.
- It is seen in 50% cases after exercise.
- Biochemical assay
- Phosphorylase reaction is absent.
Other Diagnostic Studies
Muscle Biopsy
- Muscle biopsy reveals:[14]
- Fiber size variability
- Positive subsarcolemmal blebs with periodic acid-Schiff stain
- Intermyofibril vacuoles
- Selective atrophy of type 1 muscle fibers may be seen.
Treatment
Medical Therapy
- Dietary modification
- Higher-carbohydrate diet
- High-protein intake
- Simple carbohydrates (eg, sucrose) consumption before exercise can help to improve exercise tolerance.
- Dietary supplementation with creatine can help to some extent.[15]
- Exercise
Surgery
- Surgical intervention is not recommended for the management of glycogen storage disease type V.
Primary Prevention
- Effective measures for primary prevention of glycogen storage disease type 5 include genetic counseling, prenatal diagnosis, and screening.
External links
References
- ↑ McARDLE B (1951). "Myopathy due to a defect in muscle glycogen breakdown". Clin Sci. 10 (1): 13–35. PMID 24540673.
- ↑ Bartram C, Edwards RH, Clague J, Beynon RJ (1993). "McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases". Hum. Mol. Genet. 2 (8): 1291–3. PMID 8401511.
- ↑ Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T (2015). "McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene". Hum. Mutat. 36 (7): 669–78. doi:10.1002/humu.22806. PMID 25914343.
- ↑ Nogales-Gadea G, Santalla A, Brull A, de Luna N, Lucia A, Pinós T (2015). "The pathogenomics of McArdle disease--genes, enzymes, models, and therapeutic implications". J. Inherit. Metab. Dis. 38 (2): 221–30. doi:10.1007/s10545-014-9743-2. PMID 25053163.
- ↑ Nogales-Gadea G, Brull A, Santalla A, Andreu AL, Arenas J, Martín MA, Lucia A, de Luna N, Pinós T (2015). "McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene". Hum. Mutat. 36 (7): 669–78. doi:10.1002/humu.22806. PMID 25914343.
- ↑ Lucia A, Ruiz JR, Santalla A, Nogales-Gadea G, Rubio JC, García-Consuegra I, Cabello A, Pérez M, Teijeira S, Vieitez I, Navarro C, Arenas J, Martin MA, Andreu AL (2012). "Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry". J. Neurol. Neurosurg. Psychiatry. 83 (3): 322–8. doi:10.1136/jnnp-2011-301593. PMID 22250184.
- ↑ Haller RG (2000). "Treatment of McArdle disease". Arch. Neurol. 57 (7): 923–4. PMID 10891971.
- ↑ Bollig G (2013). "McArdle's disease (glycogen storage disease type V) and anesthesia--a case report and review of the literature". Paediatr Anaesth. 23 (9): 817–23. doi:10.1111/pan.12164. PMID 23565573.
- ↑ Kazemi-Esfarjani P, Skomorowska E, Jensen TD, Haller RG, Vissing J (2002). "A nonischemic forearm exercise test for McArdle disease". Ann. Neurol. 52 (2): 153–9. doi:10.1002/ana.10263. PMID 12210784.
- ↑ Andersen ST, Dunø M, Schwartz M, Vissing J (2006). "Do carriers of PYGM mutations have symptoms of McArdle disease?". Neurology. 67 (4): 716–8. doi:10.1212/01.wnl.0000230154.79933.d7. PMID 16924035.
- ↑ Ørngreen MC, Jeppesen TD, Andersen ST, Taivassalo T, Hauerslev S, Preisler N, Haller RG, van Hall G, Vissing J (2009). "Fat metabolism during exercise in patients with McArdle disease". Neurology. 72 (8): 718–24. doi:10.1212/01.wnl.0000343002.74480.e4. PMID 19237700.
- ↑ Kitaoka Y (2014). "McArdle Disease and Exercise Physiology". Biology (Basel). 3 (1): 157–66. doi:10.3390/biology3010157. PMC 4009758. PMID 24833339.
- ↑ Braakhekke JP, de Bruin MI, Stegeman DF, Wevers RA, Binkhorst RA, Joosten EM (1986). "The second wind phenomenon in McArdle's disease". Brain. 109 ( Pt 6): 1087–101. PMID 3466659.
- ↑ Felice KJ, Grunnet ML, Sima AA (1996). "Selective atrophy of type 1 muscle fibers in McArdle's disease". Neurology. 47 (2): 581–3. PMID 8757045.
- ↑ Vorgerd M, Grehl T, Jager M, Muller K, Freitag G, Patzold T, Bruns N, Fabian K, Tegenthoff M, Mortier W, Luttmann A, Zange J, Malin JP (2000). "Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial". Arch. Neurol. 57 (7): 956–63. PMID 10891977.
- ↑ Haller RG, Wyrick P, Taivassalo T, Vissing J (2006). "Aerobic conditioning: an effective therapy in McArdle's disease". Ann. Neurol. 59 (6): 922–8. doi:10.1002/ana.20881. PMID 16718692.
- ↑ Quinlivan R, Vissing J, Hilton-Jones D, Buckley J (2011). "Physical training for McArdle disease". Cochrane Database Syst Rev (12): CD007931. doi:10.1002/14651858.CD007931.pub2. PMID 22161416.
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