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Rhabdomyolysis: a genetic perspective.

Scalco RS, Gardiner AR, Pitceathly RD, Zanoteli E, Becker J, Holton JL, Houlden H, Jungbluth H, Quinlivan R - Orphanet J Rare Dis (2015)

Bottom Line: Apart from trauma, a wide range of causes have been reported including drug abuse and infections.Each gene has been reviewed for the following: clinical phenotype, typical triggers for RM and recommended diagnostic approach.The purpose of this review is to highlight the most important features associated with specific genetic defects in order to aid the diagnosis of patients presenting with hereditary causes of recurrent RM.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK. renata_scalco@hotmail.com.

ABSTRACT
Rhabdomyolysis (RM) is a clinical emergency characterized by fulminant skeletal muscle damage and release of intracellular muscle components into the blood stream leading to myoglobinuria and, in severe cases, acute renal failure. Apart from trauma, a wide range of causes have been reported including drug abuse and infections. Underlying genetic disorders are also a cause of RM and can often pose a diagnostic challenge, considering their marked heterogeneity and comparative rarity.In this paper we review the range of rare genetic defects known to be associated with RM. Each gene has been reviewed for the following: clinical phenotype, typical triggers for RM and recommended diagnostic approach. The purpose of this review is to highlight the most important features associated with specific genetic defects in order to aid the diagnosis of patients presenting with hereditary causes of recurrent RM.

No MeSH data available.


Related in: MedlinePlus

Examples of conditions associated with RM. In individual cases both genetic and environmental factors may combine to trigger a RM event; anaesthesia-induced RM is the best characterized example. VLCAD: very long-chain acyl-CoA dehydrogenase, CPTII: carnitine palmitoyl-transferase-II, MAD: multiple acyl-CoA dehydrogenase, GSD: glycogen storage disease, tRNA: Transfer Ribonucleic Acid, DGUOK: deoxyguanosine kinase gene, RYR1: Ryanodine Receptor 1 gene, SIL1: SIL1, S. Cerevisiae, homolog of, TSEN54: tRNA splicing endonuclease 54 gene, S. cerevisiae, homolog of, DMD: Duchenne Muscular Dystrophy, BMD: Becker Muscular Dystrophy, ANO5:Anoctamin 5 gene, LGMD: Limb-girdle Muscular Dystrophy, DYSF: Dysferlin gene, FKRP: fukutin-related protein gene [1,2,4,8,62,110-113].
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Fig1: Examples of conditions associated with RM. In individual cases both genetic and environmental factors may combine to trigger a RM event; anaesthesia-induced RM is the best characterized example. VLCAD: very long-chain acyl-CoA dehydrogenase, CPTII: carnitine palmitoyl-transferase-II, MAD: multiple acyl-CoA dehydrogenase, GSD: glycogen storage disease, tRNA: Transfer Ribonucleic Acid, DGUOK: deoxyguanosine kinase gene, RYR1: Ryanodine Receptor 1 gene, SIL1: SIL1, S. Cerevisiae, homolog of, TSEN54: tRNA splicing endonuclease 54 gene, S. cerevisiae, homolog of, DMD: Duchenne Muscular Dystrophy, BMD: Becker Muscular Dystrophy, ANO5:Anoctamin 5 gene, LGMD: Limb-girdle Muscular Dystrophy, DYSF: Dysferlin gene, FKRP: fukutin-related protein gene [1,2,4,8,62,110-113].

Mentions: Rhabdomyolysis (RM) is characterised by acute and often severe skeletal muscle damage resulting in the release of intracellular muscle components into the blood stream frequently resulting in myoglobinuria and, in severe cases, acute renal failure. Diverse etiologies (Figure 1) implicated in acute RM share a common final pathway, increased intracellular free ionized calcium, leading to muscle cell death through the activation of a number of detrimental mechanisms such as enzymatic activation and prolonged muscle fibre contraction [1,2]. Different genetic defects causing various neuromuscular and metabolic disorders are known to be associated with RM. Recurrent RM, exercise related complaints and a positive family history are common features of an underlying genetic condition. In some instances, RM may be due to a combination of genetic predisposition and environmental causes. In these cases a purely environmental factor may be considered the sole cause for the acute event with a relatively high risk of recurrence if the genetic diagnosis is not considered. Recently reported examples are a number of patients with “virally-induced” RM who in fact had malignant hyperthermia susceptibility (MHS)-associated RYR1 mutations, resulting in a genetic predisposition for the virally-triggered muscle breakdown [3,4].Figure 1


Rhabdomyolysis: a genetic perspective.

Scalco RS, Gardiner AR, Pitceathly RD, Zanoteli E, Becker J, Holton JL, Houlden H, Jungbluth H, Quinlivan R - Orphanet J Rare Dis (2015)

Examples of conditions associated with RM. In individual cases both genetic and environmental factors may combine to trigger a RM event; anaesthesia-induced RM is the best characterized example. VLCAD: very long-chain acyl-CoA dehydrogenase, CPTII: carnitine palmitoyl-transferase-II, MAD: multiple acyl-CoA dehydrogenase, GSD: glycogen storage disease, tRNA: Transfer Ribonucleic Acid, DGUOK: deoxyguanosine kinase gene, RYR1: Ryanodine Receptor 1 gene, SIL1: SIL1, S. Cerevisiae, homolog of, TSEN54: tRNA splicing endonuclease 54 gene, S. cerevisiae, homolog of, DMD: Duchenne Muscular Dystrophy, BMD: Becker Muscular Dystrophy, ANO5:Anoctamin 5 gene, LGMD: Limb-girdle Muscular Dystrophy, DYSF: Dysferlin gene, FKRP: fukutin-related protein gene [1,2,4,8,62,110-113].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522153&req=5

Fig1: Examples of conditions associated with RM. In individual cases both genetic and environmental factors may combine to trigger a RM event; anaesthesia-induced RM is the best characterized example. VLCAD: very long-chain acyl-CoA dehydrogenase, CPTII: carnitine palmitoyl-transferase-II, MAD: multiple acyl-CoA dehydrogenase, GSD: glycogen storage disease, tRNA: Transfer Ribonucleic Acid, DGUOK: deoxyguanosine kinase gene, RYR1: Ryanodine Receptor 1 gene, SIL1: SIL1, S. Cerevisiae, homolog of, TSEN54: tRNA splicing endonuclease 54 gene, S. cerevisiae, homolog of, DMD: Duchenne Muscular Dystrophy, BMD: Becker Muscular Dystrophy, ANO5:Anoctamin 5 gene, LGMD: Limb-girdle Muscular Dystrophy, DYSF: Dysferlin gene, FKRP: fukutin-related protein gene [1,2,4,8,62,110-113].
Mentions: Rhabdomyolysis (RM) is characterised by acute and often severe skeletal muscle damage resulting in the release of intracellular muscle components into the blood stream frequently resulting in myoglobinuria and, in severe cases, acute renal failure. Diverse etiologies (Figure 1) implicated in acute RM share a common final pathway, increased intracellular free ionized calcium, leading to muscle cell death through the activation of a number of detrimental mechanisms such as enzymatic activation and prolonged muscle fibre contraction [1,2]. Different genetic defects causing various neuromuscular and metabolic disorders are known to be associated with RM. Recurrent RM, exercise related complaints and a positive family history are common features of an underlying genetic condition. In some instances, RM may be due to a combination of genetic predisposition and environmental causes. In these cases a purely environmental factor may be considered the sole cause for the acute event with a relatively high risk of recurrence if the genetic diagnosis is not considered. Recently reported examples are a number of patients with “virally-induced” RM who in fact had malignant hyperthermia susceptibility (MHS)-associated RYR1 mutations, resulting in a genetic predisposition for the virally-triggered muscle breakdown [3,4].Figure 1

Bottom Line: Apart from trauma, a wide range of causes have been reported including drug abuse and infections.Each gene has been reviewed for the following: clinical phenotype, typical triggers for RM and recommended diagnostic approach.The purpose of this review is to highlight the most important features associated with specific genetic defects in order to aid the diagnosis of patients presenting with hereditary causes of recurrent RM.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Neuromuscular Diseases and Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK. renata_scalco@hotmail.com.

ABSTRACT
Rhabdomyolysis (RM) is a clinical emergency characterized by fulminant skeletal muscle damage and release of intracellular muscle components into the blood stream leading to myoglobinuria and, in severe cases, acute renal failure. Apart from trauma, a wide range of causes have been reported including drug abuse and infections. Underlying genetic disorders are also a cause of RM and can often pose a diagnostic challenge, considering their marked heterogeneity and comparative rarity.In this paper we review the range of rare genetic defects known to be associated with RM. Each gene has been reviewed for the following: clinical phenotype, typical triggers for RM and recommended diagnostic approach. The purpose of this review is to highlight the most important features associated with specific genetic defects in order to aid the diagnosis of patients presenting with hereditary causes of recurrent RM.

No MeSH data available.


Related in: MedlinePlus