IllnessMalignant hyperthermia, susceptibility; differential diagnosis

NGS +

[Sanger]

As a "pharmacogenetic disorder" malignant hyperthermia is a severe reaction to certain anesthetics including anesthetic gases causing an increase in heart rate, hyperthermia, accelerated respiration, muscle rigidity, rhabdomyolysis and acidosis. Cardiac arrest and renal failure as well as disseminated intravascular coagulation can be acutely life-threatening. Affected individuals are also at some risk for "awake" malignant hyperthermia, in which the severe reaction occurs after physical activity, often while being sick. On the other hand, while malignant hyperthermia often occurs in people without other serious medical problems, Central Core and multiminicore disorders and STAC3 disorders are particularly associated with susceptibility to malignant hyperthermia. Susceptibility for maligne hyperthermia is often autosomal dominantly inherited, rarely autosomal recessively. The DNA diagnostic yield is at least 60%. Therefore, an inconspicuous molecular genetic result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1146/

• Alias: Hyperthermia of Anesthesia; Malignant Hyperpyrexia; Fulminating Hyperpyrexia 52
• Allelic: Apnea, postanesthetic, susceptibility to, due to BCHE deficiency (BCHE)
• Allelic: CPT II deficiency, lethal neonatal + infantile (CPT2)
• Allelic: Central core disease (RYR1)
• Allelic: Efavirenz central nervous system toxicity, susceptibility to (CYP2B6)
• Allelic: Efavirenz, poor metabolism of (CYP2B6)
• Allelic: Encephalopathy, acute, infection-induced, 4, susceptibility to (CPT2)
• Allelic: Hypokalemic periodic paralysis, type 1 (CACNA1S)
• Allelic: King-Denborough syndrome (RYR1)
• Allelic: Minicore myopathy with external ophthalmoplegia (RYR1)
• Allelic: Neuromuscular disease, congenital, with uniform type 1 fiber (RYR1)
• Allelic: Thyrotoxic periodic paralysis, susceptibility to, 1 (CACNA1S)
• [Medication-relevant polymorphisms in CYP2E1, CYP2B6, CYP2C9, CYP3A4, GSTP1, UGT1A9, SULT1A1, NQO1]
• Acyl-CoA dehydrogenase, medium chain, deficiency of (ACADM)
• Butyrylcholinesterase deficiency (BCHE)
• CPT II deficiency, infantile (CPT2)
• CPT II deficiency, lethal neonatal (CPT2)
• CPT II deficiency, myopathic, stress-induced (CPT2)
• Drug metabolism, altered, CYP2C8-related (CYP2C8)
• Malignant hyperthermia susceptibility 1 (RYR1)
• Malignant hyperthermia susceptibility 3 (CACNA2D1)
• Malignant hyperthermia susceptibility 5 (CACNA1S)
• McArdle disease (PYGM)
• Metabolic encephalomyop. crises, recurrent, rhabdomyolysis, cardiac arrhyth., neurodegen. (TANGO2)
• Myopathy due to myoadenylate deaminase deficiency (AMPD1)
• Myopathy, congenital, Baily-Bloch (STAC3)
• Rhabdomyolysis, cerivastatin-induced (CYP2C8)
• Statin-induced rhabdomyolysis (CYP3A4)
• Traboulsi syndrome: dislocated crystalline lenses, anterior segment abnorm, distinctive face (ASPH)