Muscle Biopsy and In Vitro  Contracture Test in Subjects with Idiopathic HyperCKemia

Malandrini, Alessandro; Orrico, Alfredo; Gaudiano, Carmen; Gambelli, Simona; Galli, Lucia; Berti, Gianna; Tegazzin, Vincenzo; Dotti, Maria Teresa; Federico, Antonio; Sorrentino, Vincenzo

doi:10.1097/aln.0b013e3181862a0d

Cited by 37 publications

(35 citation statements)

References 14 publications

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“…Of note, the p.Asp4505His variant has been previously implicated in a fatal non-pharmacologic induced MH episode, late-axial myopathy, and idiopathic hyperCKemia with MHS [20, 41, 44]. This reinforces the importance of detecting RYR1 variants, even in those with only mild myopathy-related symptoms, as such individuals can still be at risk.…”

Section: Discussionmentioning

confidence: 71%

Correlation of phenotype with genotype and protein structure in RYR1-related disorders

et al. 2018

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Variants in the skeletal muscle ryanodine receptor 1 gene (RYR1) result in a spectrum of RYR1-related disorders. Presentation during infancy is typical and ranges from delayed motor milestones and proximal muscle weakness to severe respiratory impairment and ophthalmoplegia. We aimed to elucidate correlations between genotype, protein structure and clinical phenotype in this rare disease population. Genetic and clinical data from 47 affected individuals were analyzed and variants mapped to the cryo-EM RyR1 structure. Comparisons of clinical severity, motor and respiratory function and symptomatology were made according to the mode of inheritance and affected RyR1 structural domain(s). Overall, 49 RYR1 variants were identified in 47 cases (dominant/de novo, n = 35; recessive, n = 12). Three variants were previously unreported. In recessive cases, facial weakness, neonatal hypotonia, ophthalmoplegia/paresis, ptosis, and scapular winging were more frequently observed than in dominant/de novo cases (all, p < 0.05). Both dominant/de novo and recessive cases exhibited core myopathy histopathology. Clinically severe cases were typically recessive or had variants localized to the RyR1 cytosolic shell domain. Motor deficits were most apparent in the MFM-32 standing and transfers dimension, [median (IQR) 85.4 (18.8)% of maximum score] and recessive cases exhibited significantly greater overall motor function impairment compared to dominant/de novo cases [79.7 (18.8)% vs. 87.5 (17.7)% of maximum score, p = 0.03]. Variant mapping revealed patterns of clinical severity across RyR1 domains, including a structural plane of interest within the RyR1 cytosolic shell, in which 84% of variants affected the bridging solenoid. We have corroborated genotype-phenotype correlations and identified RyR1 regions that may be especially sensitive to structural modification.Electronic supplementary materialThe online version of this article (10.1007/s00415-018-9033-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 71%

Correlation of phenotype with genotype and protein structure in RYR1-related disorders

et al. 2018

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“…Weglinski et al (28) reported that 49% of 49 patients with high CK levels had a positive CHCT. However, Malandrini et al (29) described only one MHS and one MHE patient of 37 with idiopathic hyperkalemia, or elevated serum CK levels without weaknesses or other neuromuscular symptoms. CK levels above normal (25-170 U/L) were observed in 13/104 (12.5%) and 25/90 (27.8%) of MHN and MHS patients, respectively, indicating a lack of correlation of CK levels with MH susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Use of the caffeine-halothane contracture test for the diagnosis of malignant hyperthermia in Brazil

Sudo

Cunha

Carmo

et al. 2010

Braz J Med Biol Res

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“…Electromyography and nerve conduction studies detect abnormalities in nearly half of cases of asymptomatic CK elevation, 7,21,27,28,30,31,33 but, as with biopsy, most changes are nonspecific. Although electro-myography and nerve conduction studies can help distinguish primary neuropathic from myopathic disorders, the sensitivity and specificity are low for diagnosis.…”

Section: Muscle Biopsy Electromyography and Nerve Conduction Studiesmentioning

confidence: 99%

“…Using combined muscle biopsy, electromyography, and nerve conduction studies, the likelihood of making a diagnosis in patients with asymptomatic elevated CK is 28% on average (range of studies 4%–79%), 2,7,21,26–28,30–32 and findings are nonspecific in 30% to 40% of cases. Findings are normal in about 30% to 40% of cases, which are thus diagnosed as idiopathic asymptomatic elevated CK.…”

Section: Muscle Biopsy Electromyography and Nerve Conduction Studiesmentioning

confidence: 99%

Approach to asymptomatic creatine kinase elevation

Moghadam-Kia

Oddis

Aggarwal

2016

CCJM

154

103

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How to manage a patient who has an elevated serum creatine kinase (CK) level but no or insignificant muscle-related signs and symptoms is a clinical conundrum. The authors provide a systematic approach, including repeat testing after a period of rest, defining higher thresholds over which pursuing a diagnosis is worthwhile, and evaluating for a variety of nonneuromuscular causes. They also outline a workup for neuromuscular causes.

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Muscle Biopsy and In Vitro Contracture Test in Subjects with Idiopathic HyperCKemia

Cited by 37 publications

References 14 publications

Correlation of phenotype with genotype and protein structure in RYR1-related disorders

Correlation of phenotype with genotype and protein structure in RYR1-related disorders

Use of the caffeine-halothane contracture test for the diagnosis of malignant hyperthermia in Brazil

Approach to asymptomatic creatine kinase elevation

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