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Case Report Volume 11 Issue 1
Atypical laminopathy phenotype: recurrent exertional hyperCKemia and metabolic syndrome in a patient with an LMNA c.659g>a [p.(ARG220HIS)] variant
Marah Obaid, Reem AI Refai, Hussam Abu-Farsakh
Received: September 30, 2026 | Published: October 20, 2026
Citation: Obeid M, Rifaei R, Abu-Farsakh H. Atypical laminopathy phenotype: recurrent exertional hyperCKemia and metabolic syndrome in a patient with an LMNA c.659g>a [p.(ARG220HIS)] variant. Int Clin Pathol J. 2026;11(1):54-56. DOI: 10.15406/icpjl.2026.11.00228
Abstract
Background: Pathogenic variants in LMNA cause a heterogeneous spectrum of disorders collectively known as laminopathies, encompassing familial partial lipodystrophy (FPLD), Emery–Dreifuss muscular dystrophy, dilated cardiomyopathy, and accelerated aging syndromes. Case presentation: An 18-year-old male born to consanguineous parents presented with recurrent, exercise-induced muscle cramps, episodic dark urine, and marked hyperCKemia (peak creatine kinase >10,000 U/L), along with profound metabolic syndrome characterized by marked insulin resistance (HOMA-IR >6.85), severe hypertriglyceridemia, and hepatic steatosis. Muscle histopathology revealed striking subsarcolemmal periodic acid–Schiff (PAS)-positive accumulation, strongly mimicking a glycogen storage myopathy such as McArdle disease (GSD V). However, a 210-gene targeted neuromuscular next-generation sequencing panel excluded PYGM alterations and identified a heterozygous likely pathogenic LMNA c.659G>A [p.(Arg220His)] variant (allele fraction 47%). Conclusions: Exertional rhabdomyolysis and marked hyperCKemia represent atypical clinical manifestations of LMNA alterations, especially when occurring alongside severe lipodystrophic metabolic derangements. This case highlights diagnostic overlap between metabolic myopathies and striated muscle laminopathies, demonstrating the clinical utility of comprehensive genomic profiling in resolving complex neuromuscular presentations.
Keywords: laminopathy, familial partial lipodystrophy, hyperCKemia, LMNA, Rhabdomyolysis, McArdle disease mimic
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