McArdle Disease: Difference between revisions

McArdle Disease
Synonym	Glycogen Storage Disease Type V
Inheritance	Autosomal recessive
Genetics	Biallelic pathogenic variants in PYGM gene
Clinical Features	Exercise intolerance and muscle cramps, rhabdomyolysis. Progressive muscle weakness later in life.
Tests	CK, Ischaemic forearm exercise test (low values of post-exercise plasma lactate-to-ammonia ratio), molecular genetics.

Latest revision as of 18:13, 12 March 2023

Written by: Dr Jeremy Steinberg – created: 14 February 2023; last modified: 12 March 2023

This article is still missing information.

McArdle disease (also known as glycogen storage disease type V, type V glycogenosis, or myophosophorylase deficiency) is an autosomal recessive disorder of carbohydrate metabolism. It is characterized by the absence of muscle glycogen phosphorylase resulting in impaired muscle metabolism. Glycogen phosphorylase is a key enzyme that takes part in the first step of glycogenolysis. Misdiagnoses are common even through adult years.

Pathophysiology

Glycogen phosphorylase catalyzes glycogen into glucose-1-phosphate through removing alpha-1,4-glucoside residues from the outer branches of the glycogen molecule. This degradation continues until the peripheral branches of glycogen are shortened to around 4 glucosyl units.

The muscle symptoms relate to the inability to generate energy from muscle glycogen because of deficiency of the muscle isoform of glycogen phosphorylase (PYGM). Of note, There are also liver (PYGL)and brain (PYGB) isoforms of glycogen phosphorylase, however PYGM is also expressed in non-muscular tissues.

Clinical Features

Patients cardinally experience exercise intolerance in childhood or in young adulthood with exertional muscle pain and cramps induced by brief but intense activities such as weight lifting or sprinting. However symptoms can also occur with prolonged low-intensity exercise. Exertional fatigue without pain is a feature in some patients.

In infants, symptoms may include difficulty crawling more than a few yards, while toddlers may want to be carried or put in a push-chair all the time and complain of pain when walking. In children, the disease can lead to an inability to run more than 100 meters, an inability to keep up with peers, and collapse or vomiting during sporting activities.

One hallmark of McArdle disease is the "second wind" phenomenon. During aerobic activity, patients experience a period where symptoms improve after 8-10 minutes of exercise. This is thought to be due to the mobilisation and use of blood-borne glucose.

Rhabdomyolysis/myoglobinuria can occur but usually not until the second or third decade, with approximately 50% being related to exertion. Acute renal failure can be a complication of this.

Examination is usually normal between attacks. However around one third have fixed proximal weakness due to recurrent episodes of rhabdomyolysis. Rarely it presents in late-adulthood with progressive proximal muscle atrophy rather than exercise intolerance.

Diagnosis

Diagnosis of McArdle disease involves a combination of clinical presentation, laboratory tests, and genetic testing.

Baseline serum CK is usually raised (10-15 times the normal range), while serum urate is frequently elevated.
A non-ischemic forearm exercise test shows no significant rise in lactate.
DNA analysis can identify common mutations of PYGM in Northern Europeans, such as p.Arg50X and p.Gly205Ser. Next-tier testing involves full PYGM sequencing.
Muscle biopsy is rarely required but can be done if there is no access to molecular genetics. Findings are vacuolar myopathy, sub-sarcolemmal glycogen deposition, and absent muscle glycogen phosphorylase activity.

Treatment

Treatment for McArdle disease is mainly supportive, with an emphasis on avoiding strenuous exercise and preventing muscle damage. Patients are encouraged to engage in regular low-intensity exercise, which can improve muscle function and reduce symptoms. Intense isometric exercises and maximum aerobic exercises should be avoided. Any bout of moderate exercise should be preceeded by 5-15 minutes gentle warm-up to active the second-wind effect.

Oral sucrose (75g) can result in improvement of exercise tolerance.

Resources

McArdle disease misdiagnosis - Scalco 2017.pdf - 571 KB (f)

OMIM - McArdle Disease

GeneReviews - McArdle Disease

References

Neuromuscular Disorders - Amato 2008

Literature Review

Reviews from the last 7 years: review articles, free review articles, systematic reviews, meta-analyses, NCBI Bookshelf

Articles from all years: PubMed search, Google Scholar search.

TRIP Database: clinical publications about evidence-based medicine.

Other Wikis: Radiopaedia, Wikipedia Search, Wikipedia I Feel Lucky, Orthobullets,

@@ Line 1: / Line 1: @@
-{{Partial}}
+{{Authors
+|Authors=Jeremy
+}}
+{{Condition
+|quality=Partial
+|synonym=Glycogen Storage Disease Type V
+|inheritance=Autosomal recessive
+|genetics=Biallelic pathogenic variants in PYGM gene
+|clinicalfeatures=Exercise intolerance and muscle cramps, rhabdomyolysis. Progressive muscle weakness later in life.
+|tests=CK, Ischaemic forearm exercise test (low values of post-exercise plasma lactate-to-ammonia ratio), molecular genetics.
+}}
+McArdle disease (also known as glycogen storage disease type V,  type V glycogenosis, or myophosophorylase deficiency) is an autosomal recessive disorder of carbohydrate metabolism. It is characterized by the absence of muscle glycogen phosphorylase resulting in impaired [[Skeletal Muscle|muscle]] metabolism. Glycogen phosphorylase is a key enzyme that takes part in the first step of glycogenolysis. Misdiagnoses are common even through adult years.
-McArdle disease is an autosomal recessive neuromuscular disease that is characterized by the absence of muscle glycogen phosphorylase resulting in impaired [[Skeletal Muscle|muscle]] metabolism. Glycogen phosphorylase is a key enzyme that takes part in the first step of glycogenolysis. Misdiagnoses are common even through adult years.
+== Pathophysiology ==
+Glycogen phosphorylase catalyzes glycogen into glucose-1-phosphate through removing alpha-1,4-glucoside residues from the outer branches of the glycogen molecule. This degradation continues until the peripheral branches of glycogen are shortened to around 4 glucosyl units.
+The muscle symptoms relate to the inability to generate energy from muscle glycogen because of deficiency of the muscle isoform of glycogen phosphorylase (PYGM). Of note, There are also liver (PYGL)and brain (PYGB) isoforms of glycogen phosphorylase, however PYGM is also expressed in non-muscular tissues.
 == Clinical Features ==
-Patients experience episodes of muscle pain, exercise intolerance, and tachycardia at the beginning of any physical activity and during strenuous activity, isometric muscle contraction, and/or resistance training.
+Patients cardinally experience exercise intolerance in childhood or in young adulthood with exertional muscle pain and cramps induced by brief but intense activities such as weight lifting or sprinting. However symptoms can also occur with prolonged low-intensity exercise. Exertional fatigue without pain is a feature in some patients.
 In infants, symptoms may include difficulty crawling more than a few yards, while toddlers may want to be carried or put in a push-chair all the time and complain of pain when walking. In children, the disease can lead to an inability to run more than 100 meters, an inability to keep up with peers, and collapse or vomiting during sporting activities.
-One hallmark of McArdle disease is the "second wind" phenomenon. During aerobic activity, patients experience a period where symptoms improve after 8-10 minutes of exercise. This is thought to be due to the switch from glycogen to fat as the primary energy source during exercise.
+One hallmark of McArdle disease is the "second wind" phenomenon. During aerobic activity, patients experience a period where symptoms improve after 8-10 minutes of exercise. This is thought to be due to the mobilisation and use of blood-borne glucose.
-However, severe episodes of muscle contracture can lead to rhabdomyolysis/myoglobinuria. This can cause muscle swelling and pain, discolouration of urine, collapse, and acute renal failure. Creatine kinase (CK) levels are markedly raised during these episodes, with levels between 40,000–250,000 IU/L.
+Rhabdomyolysis/myoglobinuria can occur but usually not until the second or third decade, with approximately 50% being related to exertion. Acute renal failure can be a complication of this.
+Examination is usually normal between attacks. However around one third have fixed proximal weakness due to recurrent episodes of rhabdomyolysis. Rarely it presents in late-adulthood with progressive proximal muscle atrophy rather than exercise intolerance.
 == Diagnosis ==
-Diagnosis of McArdle disease involves a combination of clinical presentation, laboratory tests, and genetic testing. Baseline serum CK is usually raised (10-15 times the normal range), while serum urate is frequently elevated. A non-ischemic forearm exercise test shows no significant rise in lactate, while DNA analysis can identify common mutations in Northern Europeans, such as p.Arg50X and p.Gly205Ser. Next-tier testing involves full PYGM sequencing. Muscle biopsy is rarely required and shows vacuolar myopathy, sub-sarcolemmal glycogen deposition, and absent muscle glycogen phosphorylase activity.
+Diagnosis of McArdle disease involves a combination of clinical presentation, laboratory tests, and genetic testing.
+* Baseline serum CK is usually raised (10-15 times the normal range), while serum urate is frequently elevated.
+* A non-ischemic forearm exercise test shows no significant rise in lactate.
+* DNA analysis can identify common mutations of PYGM in Northern Europeans, such as p.Arg50X and p.Gly205Ser. Next-tier testing involves full PYGM sequencing.
+* Muscle biopsy is rarely required but can be done if there is no access to molecular genetics. Findings are vacuolar myopathy, sub-sarcolemmal glycogen deposition, and absent muscle glycogen phosphorylase activity.
 == Treatment ==
-Treatment for McArdle disease is mainly supportive, with an emphasis on avoiding strenuous exercise and preventing muscle damage. Patients are encouraged to engage in regular low-intensity exercise, which can improve muscle function and reduce symptoms. Dietary interventions, such as a high-protein diet, can also help to minimize symptoms.
+Treatment for McArdle disease is mainly supportive, with an emphasis on avoiding strenuous exercise and preventing muscle damage. Patients are encouraged to engage in regular low-intensity exercise, which can improve muscle function and reduce symptoms. Intense isometric exercises and maximum aerobic exercises should be avoided. Any bout of moderate exercise should be preceeded by 5-15 minutes gentle warm-up to active the second-wind effect.
+Oral sucrose (75g) can result in improvement of exercise tolerance.
 == Resources ==
 {{PDF|McArdle disease misdiagnosis - Scalco 2017.pdf}}
-[[Category:Neuromuscular Disorders]]
+[https://omim.org/entry/232600 OMIM - McArdle Disease]
+[https://www.ncbi.nlm.nih.gov/books/NBK1344/ GeneReviews - McArdle Disease]
+== References ==
+Neuromuscular Disorders - Amato 2008
+[[Category:Muscle Disorders]]
+{{References}}
+{{Reliable sources}}
+[[Category:Glycogen Storage Diseases]]