MITOCHONDRIAL DISEASES & METABOLIC MYOPATHIES: P.323 A genetic basis is identified in 74% cases of paediatric hyperCKaemia without weakness

Abstract

This research aims to provide an evidence-based diagnostic approach to paediatric hyperCKaemia without weakness. Individuals presenting to the Neuromuscular Clinic at The Children's Hospital at Westmead were identified via retrospective chart review. Individuals with elevated serum creatine kinase (CK) on two or more occasions were included. Individuals with objective muscle weakness at presentation and use of medication or family history of disorders known to cause hyperCKaemia were excluded. Clinical features, diagnostic investigations and outcomes were assessed. Forty-seven individuals (10 months-16 years; 34 males, 13 females) from 43 families were included. Genetic testing was performed in 34/43. Genetic variants explaining hyperCKemia were identified in 25/34 (74%), with pathogenic/likely pathogenic variations found in 19 neuromuscular disease genes and 6 metabolic myopathy genes. Genetic diagnoses were identified via multiplex ligation-dependent probe amplification (MLPA), massively parallel sequencing (MPS), single gene testing and exome sequencing. Overall, individuals with metabolic diagnoses had higher peak serum CK than those with neuromuscular diagnoses. Serum CK levels remained persistently elevated in the neuromuscular group whilst serum CK normalized in some with a metabolic myopathy. In conclusion, 74% children presenting with hyperCKaemia without weakness have an underlying genetic cause. We therefore revise the diagnostic algorithm to recommend genetic screening as an early investigation in this challenging cohort. A genetic diagnosis informs clinical management, health surveillance and facilitates future family planning for themselves and their relatives.