Colchicine is a medication most commonly used in the treatment of gout and familial mediterannean fever. A rare complication of therapy is toxicity causing proximal myopathy and polyneuropathy. Colchicine myopathy has been associated with the coadministration of other medications with colchicine, such as statins or tacrolimus, and is more common in patients with renal impairment. Otherwise, it is unclear which patients are at greatest risk of developing this adverse drug reaction. ABCB1 is important to the metabolism of colchicine, so we speculated that it was possible that colchicine myopathy patients may have a particular genotype that is associated with this side effect. We describe two cases of colchicine myopathy which occurred with co-administration of rosuvastatin. From one case, we present the first published data on muscle MRI in this condition. We additionally present an analysis of four genetic polymorphisms in ABCB1 and transcript levels in muscle tissue, and demonstrate the descriptive finding of reduced ABCB1 transcript levels in the colchicine myopathy patients.
ObjectiveTo better characterize adult myotubularin 1 (MTM1)–related myopathy carriers and recommend a phenotypic classification.MethodsThis cohort study was performed at the NIH Clinical Center. Participants were required to carry a confirmed MTM1 mutation and were recruited via the Congenital Muscle Disease International Registry (n = 8), a traveling local clinic of the Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, NIH and Cure CMD (n = 1), and direct physician referral (n = 1). Neuromuscular examinations, muscle MRI, dynamic breathing MRI, cardiac MRI, pulmonary function tests (PFTs), physical therapy assessments including the Motor Function Measure 32 (MFM-32) scale, and X chromosome inactivation (XCI) studies were performed.ResultsPhenotypic categories were proposed based on ambulatory status and muscle weakness. Carriers were categorized as severe (nonambulatory; n = 1), moderate (minimal independent ambulation/assisted ambulation; n = 3), mild (independent ambulation but with evidence of muscle weakness; n = 4), and nonmanifesting (no evidence of muscle weakness; n = 2). Carriers with more severe muscle weakness exhibited greater degrees of respiratory insufficiency and abnormal signal on muscle imaging. Skeletal asymmetries were evident in both manifesting and nonmanifesting carriers. Skewed XCI did not explain phenotypic severity.ConclusionThis work illustrates the phenotypic range of MTM1-related myopathy carriers in adulthood and recommends a phenotypic classification. This classification, defined by ambulatory status and muscle weakness, is supported by muscle MRI, PFT, and MFM-32 scale composite score findings, which may serve as markers of disease progression and outcome measures in future gene therapy or other clinical trials.
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