Rhabdomyolysis: a genetic perspective

Scalco, R.; Gardiner, A.; Pitceathly, Robert D S; Zanoteli, Edmar; Becker, Jéfferson; Holton, Janice L.; Houlden, Henry; Jungbluth, Heinz; Quinlivan, R.

doi:10.1186/s13023-015-0264-3

Cited by 116 publications

(117 citation statements)

References 110 publications

(174 reference statements)

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“…It is characterized by acute skeletal muscle damage, subsequent marked serum elevations in muscle enzymes (particularly creatine kinase (CK)), and increased risk for acute kidney injury (AKI). The differential diagnosis of rhabdomyolysis is heterogeneous [1]. In general, two types of underlying etiologic conditions have been reported.…”

Section: Introductionmentioning

confidence: 99%

“…The second encompasses a high number of rare metabolic and neuromuscular monogenic disorders. In some cases, rhabdomyolysis may be secondary to a combination of genetic predisposition factors and environmental factors [1]. In those cases, the environmental factor may erroneously be considered as the sole etiology, with the risk that the primary genetic etiologic diagnosis is missed and rhabdomyolysis episodes may recur [1].…”

Section: Introductionmentioning

confidence: 99%

“…In the clinical setting, identification of the exact underlying monogenic diagnosis is challenging, because more than 60 monogenic genes have already been implicated in rhabdomyolysis (Table 1) [1]. In addition, in most cases of rhabdomyolysis the clinical presentation is nonspecific including elevated CK, dark urine secondary to myoglobinuria, and AKI in some cases.…”

Section: Introductionmentioning

confidence: 99%

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Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases

et al. 2017

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Background Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging, due to nonspecific presentation, the high number of causative genes, and current lack of data on the prevalence of monogenic forms. Methods We employed whole exome sequencing (WES) to reveal the percentage of rhabdomyolysis cases explained by single-gene (monogenic) mutations in one of 58 candidate genes. We investigated a cohort of 21 unrelated families with rhabdomyolysis. in whom no underlying etiology had been previously established. Results Using WES, we identified causative mutations in candidate genes in nine of the 21 families (43%). We detected disease-causing mutations in eight of 58 candidate genes, grouped into the following categories: 1) disorders of fatty acid metabolism (CPT2), 2) disorders of glycogen metabolism (PFKM and PGAM2), 3) disorders of abnormal skeletal muscle relaxation and contraction (CACNA1S, MYH3, RYR1 and SCN4A), and 4) disorders of purine metabolism (AHCY). Conclusions Our findings demonstrate a very high detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for rhabdomyolysis. These results highlight the importance of molecular genetic diagnostics for establishing an etiologic diagnosis. Because these patients are at risk for recurrent episodes of rhabdomyolysis and subsequent risk for AKI, WES allows adequate prophylaxis and treatment for these patients and their family members and enables a personalized medicine approach.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases

et al. 2017

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“…However, a normal biopsy may not definitely rule out a mitochondrial disorder. A variety of metabolites on urine or plasma amino acids can suggest mitochondrial dysfunction, and generalized aminoaciduria can support mitochondrial tubular dysfunction [11].…”

Section: Discussionmentioning

confidence: 99%

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

Zhao

Soni

et al. 2017

CEN Case Rep

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Rhabdomyolysis is characterized by the acute breakdown of skeletal muscle, resulting in the release of muscle cell contents, subsequent myoglobinuria, and in severe cases, acute renal failure. A number of etiologies have been identified in acute rhabdomyolysis, in which drugs and trauma account for the majority of cases. One etiological category that is commonly overlooked in the adult population is an underlying genetic defect. This may be challenging to diagnose due to its rarity in the adult demographic and the marked heterogeneity, often requiring a high level of clinical suspicion before investigation is pursued. Once diagnosed, however, appropriate steps can be taken to reduce future episodes of rhabdomyolysis, further renal injury, and other systemic complications. Here, we report a case of an adult patient presenting with acute rhabdomyolysis secondary to McArdle disease, a genetic disease causing defective glycogenolysis. The case highlights the importance of recognizing the potential of undiagnosed ''pediatric'' disorders in adulthood and particularly for underlying genetic causes of rhabdomyolysis.

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“…Körülbelül 90 perc közepes intenzitású terhelésnél (a maximális O 2 -felvétel, azaz a VO 2max 60-80%-ánál) a hepaticus és izomglikogén-raktárak is kiürülnek, és a glükóz helyett a lipidkatabolizmus kerül előtérbe. Hosszabb idővel az utolsó étkezés után vagy éhezés esetén is a szabad zsírsavak égetésével jut energiához az izomszövet (1. táblázat) [15,16].…”

Section: A Rhabdomyolysis Genetikai Okaimetabolikus Myopathiákunclassified

Rhabdomyolysis – Mikor vessük fel metabolikus myopathia lehetőségét? Esetismertetés és diagnosztikus algoritmus

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Rekurráló rhabdomyolysis miatt kezelt 46 éves nő esetét ismertetjük. Betegünknél a metabolikus myopathia hátteré-ben a zsírsav-oxidáció veleszületett zavarát, hosszú szénláncú acil-koenzim A-dehidrogenáz-hiányt diagnosztizáltunk, miután kóros acil-karnitin-és vizeletszervessav-profilt, valamint alacsony residualis enzimaktivitást detektáltunk, vé-gül genetikai vizsgálattal patogén eltérést igazoltunk. A dietoterápia bevezetése után sem kórházi kezelést igénylő metabolikus krízis nem fordult elő, sem myopathia nem alakult ki. Az eset kapcsán áttekintjük a rhabdomyolysis és a terhelés utáni izompanaszok differenciáldiagnosztikáját, különös tekintettel a metabolikus myopathiákra. Kiemeljük a zsírsav-oxidációs zavarok jellegzetességeit, illetve a hosszú szénláncú zsírsav-oxidációs zavarok akut ellátásának és gondozásának alapelveit. A metabolikus myopathiák csoportjába tartozó betegségek jól kezelhetőek, és a betegek számára megfelelő életminőséget biztosíthatunk, azonban az elsősorban zsírsav-oxidációs zavarokra jellemző, gyorsan kialakuló metabolikus krízis súlyos, akár halálos kimenetelű is lehet. Több, ebbe a csoportba tartozó betegség szerepel az újszülöttkorban szűrt anyagcsere-betegségek között, azonban esetünk ismertetésével is szeretnénk felhív-ni a figyelmet arra, hogy egyes esetekben az első tünetek csak felnőttkorban jelentkeznek. Ismétlődő rhabdomyolysis esetén bármely korú betegnél fel kell vetni az öröklődő anyagcserezavar lehetőségét. Orv Hetil. 2017; 158(47): 1873-1882. Kulcsszavak: rhabdomyolysis, zsírsav-oxidációs zavar, VLCAD-deficientia, izomanyagcsere Rhabdomyolysis -may it be a metabolic myopathy? Case report and diagnostic algorithmWe report the case of a 46-year-old female patient with recurrent rhabdomyolysis. In the background of her metabolic myopathy an inherited metabolic disorder of the fatty acid oxidation, very long-chain acyl-coenzyme A-dehydrogenase deficiency was diagnosed. The diagnosis was based on abnormal acyl-carnitine-and urine organic-acid profile in addition to low residual enzyme activity, and was confirmed by genetic testing. After introduction of dietotherapy metabolic crisis necessitating hospital admission has not occurred neither have fixed myopathic changes developed. We present here the differential diagnosis of rhabdomyolysis and exertional muscle complaints, with the metabolic myopathies in focus. The main features of fatty acid oxidation disorders are highlighted, acute and chronic managements of very long-chain acyl-coenzyme A-dehydrogenase deficiency are discussed. Metabolic myopathies respond well to treatment, so good quality of life can be achieved. However, especially in fatty acid oxidation disorders, a metabolic crisis may develop quickly and can be fatal, albeit rarely. Some of these disorders can be identified by newborn screening, but occasionally the symptoms may manifest only in adulthood.

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Rhabdomyolysis: a genetic perspective

Cited by 116 publications

References 110 publications

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

Rhabdomyolysis – Mikor vessük fel metabolikus myopathia lehetőségét? Esetismertetés és diagnosztikus algoritmus

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