What genetic mutation causes temporary paralysis after anesthesia?

Genetic Mutation Causing Temporary Paralysis After Anesthesia

Mutations in the butyrylcholinesterase gene (BCHE) cause temporary paralysis after anesthesia, most commonly presenting as prolonged apnea following succinylcholine administration. This pharmacogenetic condition results from inherited variants that reduce or alter the activity of butyrylcholinesterase (also called plasma cholinesterase or pseudocholinesterase), the enzyme responsible for metabolizing succinylcholine 1, 2.

Primary Genetic Mutations

The most clinically significant BCHE gene mutations include:

• K-variant (Kalow variant): The most frequently identified mutation in patients with prolonged apnea after succinylcholine, often found in heterozygous or homozygous forms 3, 4
• A-variant (atypical variant): Another common mutation that significantly reduces enzyme activity, with homozygous individuals (approximately 1 in 2,500 patients) being extremely sensitive to succinylcholine 1, 4
• Combined A and K variant mutations: Can occur together in heterozygous forms, further reducing cholinesterase activity 3

Clinical Presentation and Duration

Patients with BCHE mutations experience apnea lasting 5-15 minutes (mild cases) to 2-8 hours (severe cases) after standard succinylcholine doses, compared to the normal 3-5 minutes in unaffected individuals 4, 5. The severity correlates with genotype:

• Heterozygous carriers: Moderately prolonged paralysis (typically 15-90 minutes) 2, 5
• Homozygous recessive individuals: Severe prolongation (1-8 hours), occurring in approximately 1:1,500 to 1:3,000 of the general population 1, 5

Diagnostic Approach

When prolonged paralysis occurs after succinylcholine:

• Immediate laboratory testing: Measure plasma cholinesterase activity (normal range: 4,650-10,440 U/L); levels significantly below this range (e.g., 291 U/L or 20 μkat/L) confirm deficiency 2, 6, 5
• Dibucaine number test: Differentiates genetic variants from acquired deficiency; abnormal results confirm inherited enzyme abnormality 3
• Genetic analysis: PCR-based testing identifies specific BCHE mutations (A-variant, K-variant, or combinations) 3, 4
• Rule out acquired causes: Exclude pregnancy, liver disease, malignant tumors, infections, burns, or medications that reduce cholinesterase activity (oral contraceptives, organophosphate exposure, certain chemotherapy agents) 1, 6

Management Protocol

There is no specific antidote for butyrylcholinesterase deficiency; management consists of maintaining mechanical ventilation until spontaneous recovery occurs 6, 5:

• Primary treatment: Continue assisted ventilation with 100% oxygen until neuromuscular function fully recovers 6, 5
• Supportive measures: Naloxone and atropine may accelerate recovery in some cases 2
• Fresh frozen plasma transfusion: Contains functional cholinesterase and can be administered (150 mL or more) to provide enzyme replacement, though spontaneous recovery is safer 6, 5
• Avoid reversal attempts: Do not administer anticholinesterase drugs (neostigmine) as they will prolong, not reverse, the paralysis 1

Critical Prevention Strategies

Once diagnosed, patients and family members must be counseled about lifelong anesthetic implications:

• Family screening: Test first-degree relatives for plasma cholinesterase activity, as this follows autosomal recessive inheritance 2, 6
• Medical alert documentation: Patients must carry identification stating their BCHE deficiency and avoid succinylcholine in all future anesthetics 2, 6
• Alternative agents: Use non-depolarizing neuromuscular blockers (rocuronium, vecuronium) instead of succinylcholine for future procedures 1
• Avoid cholinesterase inhibitors: Patients have heightened sensitivity to organophosphate insecticides and certain medications that inhibit cholinesterase 1, 2

Important Clinical Caveats

• Preoperative screening limitations: Routine preoperative cholinesterase testing is not standard practice; most cases are discovered only after prolonged paralysis occurs 2, 6
• Previous uneventful anesthetics do not exclude risk: Patients may have received succinylcholine previously without incident if doses were lower or clinical observation was less rigorous 4, 5
• Neuromuscular monitoring is essential: Objective monitoring during first anesthetic exposure can identify abnormal responses early 4
• Ethnic variation: Novel BCHE mutations may be associated with specific ethnic populations, and genetic testing availability varies by country 6

This condition is distinct from malignant hyperthermia, which involves mutations in the ryanodine receptor gene (RYR1) and presents with hypermetabolic crisis rather than isolated prolonged paralysis 7.