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Exercise-induced muscle cramps

MedGen UID:
Concept ID:
Synonyms: Exercise-induced muscle cramping; Muscle cramps with exercise; Muscle cramps with exertion
HPO: HP:0003710


Sudden and involuntary contractions of one or more muscles brought on by physical exertion. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Exercise-induced muscle cramps

Conditions with this feature

Glycogen storage disease, type V
MedGen UID:
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Disease or Syndrome
Glycogen storage disease type V (GSDV, McArdle disease) is a metabolic myopathy characterized by exercise intolerance manifested by rapid fatigue, myalgia, and cramps in exercising muscles. Symptoms are usually precipitated by isometric exercise or sustained aerobic exercise. Most individuals improve their exercise tolerance by exploiting the "second-wind" phenomenon with relief of myalgia and fatigue after a few minutes of rest. Age of onset is frequently in the first decade of life but can vary; however, diagnosis is typically delayed as myalgia and fatigability are dismissed/overlooked. Fixed muscle weakness occurs in approximately 25% of affected individuals, is more likely to involve proximal muscles, and is more common in individuals of advanced age. Approximately 50% of affected individuals have recurrent episodes of myoglobinuria that can – on occasion – eventually result in acute renal failure.
Glycogen storage disease, type VII
MedGen UID:
Concept ID:
Disease or Syndrome
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.
Elevated circulating creatine kinase concentration
MedGen UID:
Concept ID:
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Glycogen storage disease type X
MedGen UID:
Concept ID:
Disease or Syndrome
Phosphoglycerate mutase deficiency is a disorder that primarily affects muscles used for movement (skeletal muscles). Beginning in childhood or adolescence, affected individuals experience muscle aches or cramping following strenuous physical activity. Some people with this condition also have recurrent episodes of myoglobinuria. Myoglobinuria occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin, which is processed by the kidneys and released in the urine. If untreated, myoglobinuria can lead to kidney failure.\n\nIn some cases of phosphoglycerate mutase deficiency, microscopic tube-shaped structures called tubular aggregates are seen in muscle fibers. It is unclear how tubular aggregates are associated with the signs and symptoms of the disorder.
Dihydropyrimidinase deficiency
MedGen UID:
Concept ID:
Disease or Syndrome
Dihydropyrimidinase deficiency (DPYSD) is an autosomal recessive disease characterized by the presence of dihydropyrimidinuria. The clinical phenotype is highly variable, ranging from early infantile onset of severe neurologic involvement, dysmorphic features, and feeding problems to late onset of mild intellectual disability and even asymptomatic individuals. Patients with a complete or partial deficiency have an increased risk of developing severe toxicity after administration of the anticancer drug 5-fluorouracil (5-FU) (summary by Nakajima et al., 2017). See also dihydropyrimidine dehydrogenase deficiency (274270), a similar disorder.
Danon disease
MedGen UID:
Concept ID:
Disease or Syndrome
Danon disease is a multisystem condition with predominant involvement of the heart, skeletal muscles, and retina, with overlying cognitive dysfunction. Males are typically more severely affected than females. Males usually present with childhood onset concentric hypertrophic cardiomyopathy that is progressive and often requires heart transplantation. Rarely, hypertrophic cardiomyopathy can evolve to resemble dilated cardiomyopathy. Most affected males also have cardiac conduction abnormalities. Skeletal muscle weakness may lead to delayed acquisition of motor milestones. Learning disability and intellectual disability, most often in the mild range, are common. Additionally, affected males can develop retinopathy with subsequent visual impairment. The clinical features in females are broader and more variable. Females are more likely to have dilated cardiomyopathy, with a smaller proportion requiring heart transplantation compared to affected males. Cardiac conduction abnormalities, skeletal muscle weakness, mild cognitive impairment, and pigmentary retinopathy are variably seen in affected females.
Rippling muscle disease 2
MedGen UID:
Concept ID:
Disease or Syndrome
Hereditary rippling muscle disease is an autosomal dominant disorder characterized by mechanically triggered contractions of skeletal muscle. In rippling muscle disease, mechanical stimulation leads to electrically silent muscle contractions that spread to neighboring fibers that cause visible ripples to move over the muscle. RMD is usually inherited as an autosomal dominant trait, but autosomal recessive inheritance has also been reported (Kubisch et al., 2005). Genetic Heterogeneity of Rippling Muscle Disease Another locus for RMD, designated RMD1 (600332), maps to chromosome 1q41.
Brody myopathy
MedGen UID:
Concept ID:
Disease or Syndrome
Brody disease (BROD) is an autosomal recessive skeletal muscle disorder characterized by exercise-induced muscle stiffness and cramps primarily affecting the arms, legs, and eyelids, although more generalized muscle involvement may also occur. Symptom onset is most often in the first decade, but many patients present and are diagnosed later in life. Skeletal muscle biopsy typically shows variation in fiber size, increased internal nuclei, and atrophy of type II muscle fibers. Rare patients have been reported to develop malignant hyperthermia after administration of anesthesia, suggesting that patients with the disorder should be tested. The disorder results from defective relaxation of fast-twitch (type II) skeletal muscle fibers due to defects in calcium homeostasis and reuptake in the muscle fiber (summary by Odermatt et al., 2000 and Molenaar et al., 2020).
Rippling muscle disease 1
MedGen UID:
Concept ID:
Disease or Syndrome
Metabolic myopathy due to lactate transporter defect
MedGen UID:
Concept ID:
Disease or Syndrome
A rare metabolic myopathy with characteristics of muscle cramping and/or stiffness after exercise (especially during heat exposure), post-exertional rhabdomyolysis and myoglobinuria and elevation of serum creatine kinase. Caused by mutation in the SLC16A1 gene.
Glycogen storage disease due to phosphoglycerate kinase 1 deficiency
MedGen UID:
Concept ID:
Disease or Syndrome
Phosphoglycerate kinase-1 deficiency is an X-linked recessive condition with a highly variable clinical phenotype that includes hemolytic anemia, myopathy, and neurologic involvement. Patients can express 1, 2, or all 3 of these manifestations (Shirakawa et al., 2006).
Muscular dystrophy, limb-girdle, autosomal recessive 23
MedGen UID:
Concept ID:
Disease or Syndrome
The clinical manifestations of LAMA2 muscular dystrophy (LAMA2-MD) comprise a continuous spectrum ranging from severe congenital muscular dystrophy type 1A (MDC1A) to milder late-onset LAMA2-MD. MDC1A is typically characterized by neonatal profound hypotonia, poor spontaneous movements, and respiratory failure. Failure to thrive, gastroesophageal reflux, aspiration, and recurrent chest infections necessitating frequent hospitalizations are common. As disease progresses, facial muscle weakness, temporomandibular joint contractures, and macroglossia may further impair feeding and can affect speech. In late-onset LAMA2-MD onset of manifestations range from early childhood to adulthood. Affected individuals may show muscle hypertrophy and develop a rigid spine syndrome with joint contractures, usually most prominent in the elbows. Progressive respiratory insufficiency, scoliosis, and cardiomyopathy can occur.
Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis
MedGen UID:
Concept ID:
Disease or Syndrome
Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis (MMCKR) is an autosomal recessive disorder of skeletal muscle characterized by the onset of muscle cramping and stiffness on exertion in infancy or early childhood, although later (even adult) onset has also been reported. The features remit with rest, but some individuals develop mild proximal or distal muscle weakness. Rare affected individuals may demonstrate cardiac involvement, including left ventricular dysfunction or rhythm abnormalities. Laboratory studies show increased baseline serum creatine kinase levels with episodic spikes that may coincide with rhabdomyolysis. EMG shows myopathic changes, and muscle biopsy shows nonspecific myopathic or degenerative features (Lopes Abath Neto et al., 2021; Salzer-Sheelo et al., 2022).

Professional guidelines


Dijkstra JN, Boon E, Kruijt N, Brusse E, Ramdas S, Jungbluth H, van Engelen BGM, Walters J, Voermans NC
Pract Neurol 2023 Feb;23(1):23-34. Epub 2022 Dec 15 doi: 10.1136/pn-2022-003574. PMID: 36522175
Sinha T, David AK
Am Fam Physician 2003 Feb 15;67(4):769-74, 675. PMID: 12613731
Bentley S
Sports Med 1996 Jun;21(6):409-20. doi: 10.2165/00007256-199621060-00003. PMID: 8784961

Recent clinical studies


Cleary M, Ruiz D, Eberman L, Mitchell I, Binkley H
J Sport Rehabil 2007 Aug;16(3):244-59. doi: 10.1123/jsr.16.3.244. PMID: 17923731
Orimo S, Araki M, Ishii H, Ikeda M, Kurosawa T, Arai M, Hiyamuta E
J Neurol 1987 Aug;234(6):424-6. doi: 10.1007/BF00314090. PMID: 3655846


Craighead DH, Shank SW, Gottschall JS, Passe DH, Murray B, Alexander LM, Kenney WL
Muscle Nerve 2017 Sep;56(3):379-385. Epub 2017 May 9 doi: 10.1002/mus.25611. PMID: 28192854Free PMC Article
Vissing J, Schmalbruch H, Haller RG, Clausen T
Ann Neurol 1999 Aug;46(2):274-7. PMID: 10443898

Clinical prediction guides

Ricci G, Bertolucci F, Logerfo A, Simoncini C, Papi R, Franzoni F, Dell'Osso G, Servadio A, Masoni MC, Siciliano G
Acta Myol 2015 Dec;34(2-3):120-125. PMID: 27199539Free PMC Article

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