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RYR1-Related Rhabdomyolysis: A Spectrum of Hypermetabolic States Due to Ryanodine Receptor Dysfunction
- Source :
- Current Pharmaceutical Design, 28, 2-14, Current Pharmaceutical Design, 28, 1, pp. 2-14
- Publication Year :
- 2022
-
Abstract
- Variants in the ryanodine receptor-1 gene (RYR1) have been associated with a wide range of neuromuscular conditions, including various congenital myopathies and malignant hyperthermia (MH). More recently, a number of RYR1 variants, mostly MH-associated, have been demonstrated to contribute to rhabdomyolysis events not directly related to anesthesia in otherwise healthy individuals. This review focuses on RYR1-related rhabdomyolysis in the context of several clinical presentations (i.e., exertional rhabdomyolysis, exertional heat illnesses and MH), and conditions involving a similar hypermetabolic state, in which RYR1 variants may be present (i.e., neuroleptic malignant syndrome and serotonin syndrome). The variety of triggers that can evoke rhabdomyolysis, on their own or in combination, as well as the number of potentially associated complications, illustrates that this is a condition relevant to several medical disciplines. External triggers include but are not limited to strenuous physical exercise, especially if unaccustomed or performed under challenging environmental conditions (e.g., high ambient temperature or humidity), alcohol/illicit drugs, prescription medication (in particular statins, other anti-lipid agents, antipsychotics and antidepressants) infection, or heat. Amongst all patients presenting with rhabdomyolysis, genetic susceptibility is present in a proportion, with RYR1 being one of the most common genetic causes. Clinical clues for a genetic susceptibility include recurrent rhabdomyolysis, creatine kinase (CK) levels above 50 times the upper limit of normal, hyperCKemia lasting for 8 weeks or longer, drug/medication doses insufficient to explain the rhabdomyolysis event, and positive family history. For the treatment or prevention of RYR1-related rhabdomyolysis, the RYR1 antagonist dantrolene can be administered, both in the acute phase or prophylactically in patients with a history of muscle cramps and/or recurrent rhabdomyolysis events. Aside from dantrolene, several other drugs are being investigated for their potential therapeutic use in RYR1-related disorders. These findings offer further therapeutic perspectives for humans, suggesting an important area for future research.
- Subjects :
- medicine.medical_specialty
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
Serotonin syndrome
Dantrolene
Rhabdomyolysis
Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
Internal medicine
Drug Discovery
medicine
Humans
Genetic Predisposition to Disease
Exercise
Pharmacology
biology
business.industry
Malignant hyperthermia
Ryanodine Receptor Calcium Release Channel
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
medicine.disease
Neuroleptic malignant syndrome
Mutation
biology.protein
Exertional rhabdomyolysis
Creatine kinase
medicine.symptom
business
Malignant Hyperthermia
Muscle cramp
medicine.drug
Subjects
Details
- ISSN :
- 13816128
- Database :
- OpenAIRE
- Journal :
- Current Pharmaceutical Design, 28, 2-14, Current Pharmaceutical Design, 28, 1, pp. 2-14
- Accession number :
- edsair.doi.dedup.....af702f1a9b93396e06196ac883021eb3