Recent advances in our understanding of genetic rhabdomyolysis

Cabrera‐Serrano, Macarena; Ravenscroft, Gianina

doi:10.1097/wco.0000000000001096

Cited by 10 publications

(12 citation statements)

References 64 publications

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Section: Introductionmentioning

confidence: 99%

“…Rhabdomyolysis (RM) is a complex medical disorder involving catastrophic failure of skeletal muscle homeostasis and integrity, resulting in muscle breakdown and release of muscle cytosolic content into circulation (Cabrera-Serrano & Ravenscroft, 2022). Rhabdomyolysis can give rise to serious health complications such as myoglobinuria, cardiac arrhythmia and acute kidney injury.…”

Section: Introductionmentioning

confidence: 99%

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Glycerolipid defects in skeletal muscle contribute to rhabdomyolysis in Tango2 deficiency

Casey

Kim

Tao

et al. 2022

Preprint

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Rhabdomyolysis is a clinical emergency characterized by severe muscle damage resulting in the release of intracellular muscle components leading to myoglobinuria and in severe cases, acute kidney failure. Rhabdomyolysis is caused by genetic factors that are linked to increased disease susceptibility in response to extrinsic triggers. Recessive mutations inTANGO2result in episodic rhabdomyolysis, metabolic crises, encephalopathy and cardiac arrhythmia, the underlying mechanism contributing to disease onset in response to specific triggers remains unclear. To address these challenges, we created a zebrafish model of Tango2 deficiency. Here we show that loss of Tango2 in zebrafish results in growth defects, early lethality and increased susceptibility of muscle defects similar toTANGO2patients. Detailed analyses of skeletal muscle revealed defects in the sarcoplasmic reticulum and mitochondria at the onset of disease development. The sarcoplasmic reticulum (SR) constitutes the primary lipid biosynthesis site and regulates calcium handling in skeletal muscle to control excitation-contraction coupling. Tango2 deficient SR exhibits increased sensitivity to calcium release that was partly restored by inhibition of Ryr1-mediated Ca2+release in skeletal muscle. Using lipidomics, we identified alterations in the glycerolipid state oftango2mutants which is critical for membrane stability and energy balance. Therefore, these studies provide insight into key disease processes in Tango2 deficiency and increased our understanding of how specific defects can predispose to environmental triggers in TANGO2-related disorders.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glycerolipid defects in skeletal muscle contribute to rhabdomyolysis in Tango2 deficiency

Casey

Kim

Tao

et al. 2022

Preprint

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“…Regarding dystrophies, it started with dystrophinopathy and now includes ANO5, CAV3, FKRP, SGCA, and GMPPB. 17 Recessive mutations in LPIN1, as seen in a patient in the study by Wong et al, 14 have more recently been found to be a common cause of childhood-onset and severe rhabdomyolysis in the setting of catabolic stress. For example, Kahraman et al 18 reported a 5-yearold with fatal rhabdomyolysis with ventricular tachycardia and a 7-year-old with severe rhabdomyolysis, supraventricular tachycardia, and compartment syndrome.…”

Section: Hyperckemia and Rhabdomyolysismentioning

confidence: 96%

“…Regarding dystrophies, it started with dystrophinopathy and now includes ANO5, CAV3, FKRP, SGCA, and GMPPB. 17…”

Section: Hyperckemia and Rhabdomyolysismentioning

confidence: 99%

“…Rhabdomyolysis was seen in a few of the patients reported by Wong et al 14 Advances in the genetics of rhabdomyolysis was recently presented by Cabrera-Serrano and Ravenscroft. 17 This diagnosis is used very loosely by many clinicians and really should be reserved for those with CK levels above 5 times the upper limit of normal, myoglobinuria, and typically symptoms of muscle pain, swelling, and possibly weakness. There is often a trigger such as exercise, infection, drug, or toxin.…”

Section: Hyperckemia and Rhabdomyolysismentioning

confidence: 99%

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What Is in the Myopathy Literature?

Lacomis

2023

Journal of Clinical Neuromuscular Disease

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This update begins with the results of a positive trial of intravenous immunoglobulin in dermatomyositis and a study of molecular and morphologic patterns in inclusion body myositis that may explain treatment refractoriness. Single center reports of muscular sarcoidosis and immunemediated necrotizing myopathy follow. There is also a report of caveolae-associated protein 4 antibodies as a potential biomarker and cause of immune rippling muscle disease. The remainder covers updates on muscular dystrophies as well as congenital and inherited metabolic myopathies with an emphasis on genetic testing. Rare dystrophies, including one involving ANXA11 mutations and a series on oculopharyngodistal myopathy, are discussed.

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COL4A2‐Related Disorder Presenting in Adulthood With Rhabdomyolysis

Olarewaju,

Tejon,

Shurrab

et al. 2024

American J of Med Genetics Pt A

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The alpha 1 and 2 chains of type IV collagen, encoded by the COL4A1 (MIM 120130) and COL4A2 (MIM 120090) respectively, play essential roles in the vascular basement membranes. Pathogenic variants in COL4A1/ COL4A2 are associated with autosomal dominant cerebral angiopathies. The clinical manifestations of COL4A1/COL4A2‐related disorders include: aneurysms, intracerebral hemorrhage, polymicrogyria, porencephaly, heterotopia, periventricular leukomalacia, epilepsy, and neurodevelopmental disorders. COL4A1 pathogenic variants that are in exons 24 and 25 have been associated with hereditary angiopathy, nephropathy, aneurysms, and cramps. The multisystemic phenotypes of COL4A1/COL4A2‐related disorders are increasingly being studied. Animal models have suggested that COL4A2‐related disorders may also manifest with a variable combination of multisystemic abnormalities affecting the eyes, muscles, and kidneys. Okano and colleagues recently reported a case of recurrent episodes of rhabdomyolysis in a 2‐year‐old with COL4A1‐related disorder raising fundamental questions on mechanisms of COL4A1/COL4A2 variants in muscle homeostasis. To date, rhabdomyolysis has not been associated with COL4A2‐related disorder in humans. Rhabdomyolysis is a medical emergency, where there is elevated creatine kinase (CK) level in the blood and increased excretion of myoglobin in urine, due to skeletal muscle damage and release of intracytoplasmic proteins into systemic circulation. Rhabdomyolysis is a serious medical condition. It require intensive care management due to an increased risk of some life‐threatening complications [including disseminated intravascular coagulation, renal failure, and severe hyperkalemia]. Herein, we report a case of rhabdomyolysis in an adult with COL4A2‐related structural brain malformations (including polymicrogyria and heterotopia).

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Recent advances in our understanding of genetic rhabdomyolysis

Cited by 10 publications

References 64 publications

Glycerolipid defects in skeletal muscle contribute to rhabdomyolysis in Tango2 deficiency

Glycerolipid defects in skeletal muscle contribute to rhabdomyolysis in Tango2 deficiency

What Is in the Myopathy Literature?

COL4A2‐Related Disorder Presenting in Adulthood With Rhabdomyolysis

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