Black Urine after Surgery: Rare Cause of Rhabdomyolysis and Malignant Hyperthermia Syndrome (MHS)

Introduction: Mutations in RyR1, DHP, SH3 and STAC3 predispose to MHS by increasing cytosolic calcium levels. Most mutations are AD with incomplete penetrance explaining phenotypic differences. RyR1 is a Ca channel located on skeletal muscle sarcoplasmic reticulum, mediates calcium influx for muscle contraction. Activating RyR1mutations cause sustained calcium influx, muscle contraction and hypermetabolism, acidosis, hyperthermia and rhabdomyolysis, following exposure to volatile anesthetics +/- succinylcholine. In addition to MHS, RyR1 mutation has been associated with Central Core Disease, Multi-minicore disease, Centronuclear myopathy, congential fiber-type disproportion and predispose to statin-induced myopathy and exertion induced rhabdomyolysis Case Description: 49 y/o Caucasian male s/p bony hearing aid placement for congenital mixed hearing loss developed black urine, myalgia and masseter spasm in the immediate postop period after iv succinylcholine 120 mg and propofol anesthesia. He described dark urine post OR in 2015, proximal muscle weakness after exertion, lifelong muscle cramps, + FHx of cramps, previous uncomplicated anasthesia for appendectomy at 18yr. Dipstick urinalysis revealed large hematuria, proteinuria & 3-10 RBC on microscopy, with large myoglobin. Post OR CPK was 14143U/L, peaked at 74320U/L POD1 and improved to 2682U/l on POD 5 with aggressive IVF. Electrolytes and creatinine remained normal, improving hepatic transaminitis. Whole genome sequencing revealed heterozygous, pathogenic variant in the RYR1, specifically c.1840C>T(p. Arg614Cys) Discussion: Pathogenic variant in RYR1 are the commonest genetic causes of MHS, wide spectrum neuromuscular disorders and congenital myopathies. MHS is characterized by a severe reaction to specific anesthetic drugs, a result of uncontrolled skeletal muscle hypermetabolism. Symptoms are preceded by specific anesthetics, with or without depolarizing muscle relaxant, like succinylcholine. Affected individuals can have severe muscle rigidity or spasms, cardiac arrhtymias, hyperthemia, rhabdomyolysis. Rarely, at risk patients demonstrate symptoms after intense physical activity. Contracture test with caffeine-halothane with high sensitivity may be used for screening. Genetic testing may not identify all involved genes, avoidance of triggers may be preferred.Treatment includes dantrolene, electrolytes management and aggressive IVF