A genetic basis is identified in 74% cases of paediatric hyperCKaemia without weakness presenting to a tertiary paediatric neuromuscular centre

Wong, Wui‐Kwan; Bryen, Samantha J; Bournazos, Adam; Yasa, Joe; Lemckert, Frances A.; Bommireddipall, Shobhana; Waddell, Leigh B.; Menezes, Manoj P.; Webster, Richard; Davis, Mark; Liang, Christina; Cooper, Sandra T.; Jones, Kristi

doi:10.1016/j.nmd.2022.07.401

Cited by 4 publications

(4 citation statements)

References 29 publications

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“…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.…”

Section: Hyperckemia and Rhabdomyolysismentioning

confidence: 97%

“…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: 98%

“…Dubey et al 13 recently reported the presence of cavin-4 IgG in the serum of patients with RMD, and this antibody may be a biomarker of immune-mediated rippling muscle disease (iRMD). 14 The authors examined serum from 10 adults who were previously diagnosed with iRMD. Using human proteome phage immunoprecipitation sequencing, they identified an IgG autoantibody against caveolae-associated protein 4 (cavin–4) in 8 of the 10 patients.…”

Section: Autoimmune Myopathiesmentioning

confidence: 99%

“…In adults, the diagnostic yield of EDx and muscle biopsy ranges from 8% to 55%. [14][15][16] A diagnosis is more likely in children. 15 As more comprehensive genetic testing becomes available, it would seem likely that the diagnostic yield will increase and genetic testing will be used first line, especially in children.…”

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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Section: Hyperckemia and Rhabdomyolysismentioning

confidence: 97%

Section: Hyperckemia and Rhabdomyolysismentioning

confidence: 98%

Section: Autoimmune Myopathiesmentioning

confidence: 99%

Section: Hyperckemia and Rhabdomyolysismentioning

confidence: 99%

See 2 more Smart Citations

What Is in the Myopathy Literature?

Lacomis

2023

Journal of Clinical Neuromuscular Disease

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Asymptomatic HyperCKemia in the Pediatric Population

Marti,

Pitarch-Castellano,

Muelas

et al. 2025

Neurology

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Background and ObjectivesPersistent elevation of serum creatine kinase levels (hyperCKemia) as an isolated manifestation presents a diagnostic challenge. Genetic myopathies are frequently involved; however, studies using next-generation sequencing (NGS) in pediatric patients are lacking, and the significance of genetic aberrations remains poorly understood. This study, therefore, aimed to investigate the relevance of NGS and the support of contemporary diagnostic tools in the diagnosis of pediatric asymptomatic hyperCKemia.MethodsThis was a prospective cohort study enrolling pediatric (0–18 years old) patients meeting the predefined criteria for asymptomatic/paucisymptomatic hyperCKemia, excluding DMD gene deletion/duplication, recruited from a referral center. NGS, muscle MRI, EMG, and muscle biopsies with immunolabeling and inflammatory markers were performed according to a prespecified protocol. Data analysis was performed using descriptive/univariate statistics and Bayesian logistic regression.ResultsThe series comprised 65 patients (78% male). NGS diagnosis was achieved in 55% of the cohort, with 70% of the pathogenic variants involving 7 genes (DMD, CAPN3, ANO5, DYSF, RYR1, GAA, and CAV3). The diagnostic rate was similar across all age groups; however, the gene profiles varied between the childhood and juvenile groups. EMG yielded myopathic features in 48% of the investigated cases, being predictive for diagnosis (p < 0.05; odds ratio [OR] 13.484, 95% CI 1.358–705.297). MRI showed normal (64%), focal fatty change (26%), or short-tau inversion recovery hyperintensity (10%) profiles, which were not predictive of diagnosis but supported muscle biopsy indications. Muscle biopsy provided a significant diagnostic effect (p < 0.05; OR 0.028, 95% CI 0.001–0.238), contributing to myopathologic features clarifying the variant pathogenicity and identifying inflammatory myopathies. The diagnoses remained inconclusive and unresolved in 14% and 29% of the cohorts, respectively. The diagnostic rate for patients with CK levels below the threshold of 3× was 42%. In multivariate analysis, NGS was the only variable achieving a significant diagnostic effect (β = 9.85, 95% CI 4.65–16.09).DiscussionNGS, as the primary diagnostic tool for investigating hyperCKemia in the pediatric population, yielded a higher diagnostic rate. However, muscle biopsies are necessary to define variants of uncertain pathogenicity and aid in identifying inflammatory myopathies. EMG and MRI may play a role in hyperCKemia characterization, guiding the decision to perform muscle biopsy. The primary limitation of this study was that not all ancillary tests were performed in all recruited patients owing to ethical restrictions, which lowered the power of the predictive analysis.

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Multicentric Study on the Diagnostic of Neuromuscular Diseases in Children with High Creatinine Phosphokinase Levels

Monteiro,

Garrido,

Pereira

et al. 2024

Children

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Background: Neuromuscular diseases (NMDs) are rare, predominantly hereditary, with progressive course disorders. Furthermore, diagnosis can be delayed by years after symptoms emerge, resulting in missed opportunities for modifying disease progression, specific therapeutic approaches, and counseling. Some NMDs have high levels of creatine phosphokinase (CK). Thus, its measurement can indicate an NMD associated with muscle involvement. Objectives: We aimed to identify myopathies and muscular dystrophies through elevated CK levels for early detection of these disorders. Methods: A prospective, observational, and analytical study of children and teenagers showing high levels of CK, showing mild symptoms, or who were asymptomatic with elevation of transaminases from all pediatric units in the north of Portugal was performed. All diagnosed patients were referred to our Center for Neuromuscular Diseases. Additionally, CK level confirmation, clinical examination, and investigation were performed according to best-practice clinical guidelines. Results: We found 33 patients from 8/12 pediatric units. A diagnosis with implications for care measures and treatment was performed in half of the patients. A total of 30% presented an NMD diagnosis. Dystrophinopathies represented the largest group (21%). Conclusions: Therefore, NMDs should be considered in children and teenagers with high CK levels, even those with mild symptoms. Screening for CK elevation should be used to promote an earlier diagnosis of many NMDs.

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A genetic basis is identified in 74% cases of paediatric hyperCKaemia without weakness presenting to a tertiary paediatric neuromuscular centre

Cited by 4 publications

References 29 publications

What Is in the Myopathy Literature?

What Is in the Myopathy Literature?

Asymptomatic HyperCKemia in the Pediatric Population

Multicentric Study on the Diagnostic of Neuromuscular Diseases in Children with High Creatinine Phosphokinase Levels

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