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Review
. 2015 May 2:10:51.
doi: 10.1186/s13023-015-0264-3.

Rhabdomyolysis: a genetic perspective

Renata Siciliani Scalco  1   2   3 , Alice R Gardiner  4 , Robert Ds Pitceathly  5   6 , Edmar Zanoteli  7 , Jefferson Becker  8 , Janice L Holton  9 , Henry Houlden  10 , Heinz Jungbluth  11   12   13 , Ros Quinlivan  14   15
Affiliations
Review

Rhabdomyolysis: a genetic perspective

Renata Siciliani Scalco et al. Orphanet J Rare Dis. .

Abstract
in English, Portuguese

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.

A rabdomiólise (RM) é um evento agudo e grave, caracterizado por danos do músculo esquelético com a liberação, em grande quantidade, de componentes intracelulares para a corrente sanguínea. Uma vasta gama de causas tem sido relatada, incluindo trauma, abuso de drogas e infecções. Doenças hereditárias também podem causar RM, mas muitas vezes representam um desafio diagnóstico, considerando a sua heterogeneidade e raridade. Por fim, diversas doenças neuromusculares costumam estar associadas com níveis de CK cronicamente elevados, dificultando a identificação correta dos episódios de RM.

Nesse artigo, revisamos os diversos defeitos genéticos associados à RM. Cada gene foi revisado abrangendo os seguintes: fenótipo clínico, gatilhos para RM e abordagem diagnóstica. O objetivo desta revisão é destacar as características mais importantes associados a defeitos genéticos específicos, a fim de auxiliar o diagnóstico de pacientes com causas hereditárias de RM recorrente.

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Figures

Figure 1
Figure 1
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].
Figure 2
Figure 2
Examples of different triggers of rhabdomyolysis. The identification of triggers may help guiding genetic testing and may also aid the interpretation of variants of uncertain significance identified on next generation sequencing in patients presenting with RM. CK: creatine kinase, 12MWT: 12 minute walk test, FBC: full blood count, MRI: magentic resonance imaging.
Figure 3
Figure 3
Muscle biopsy patterns associated with hereditary causes of RM. Muscle biopsy features may provide a guide to targeted genetic testing.
See this image and copyright information in PMC

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