Discussion

Jervell-Lange-Nielsen syndrome is a rare disease included within congenital long QT syndromes. It is an inherited disease with an autosomal recessive pattern (family pedigree in Fig. 2) caused by homozygous or compound heterozygous mutations in the KCNQ1 or KCNE1 genes, which encode components of the IKs channel. It presents an aggressive course, with approximately 50% death rate before the age of 15 years in untreated patients.^{Reference Schwartz Peter, Carla and Lia1} Along with the prolongation of the QT interval, affected individuals present with bilateral sensorineural deafness due to dysfunction of the IKs channels, which maintain the endocochlear potential in the endolymph. IKs are also found in gastric parietal cells where they participate in the secretion of hydrochloric acid. IKs channels impairment produces achlorhydria, secondary hypergastrinemia, and iron deficiency anemia, since an acidic pH is required for the correct absorption of iron.^{Reference Rice, Dickson and Lane2}

Figure 2.

Family pedigree of the index case.

Treatment of Jervell-Lange-Nielsen syndrome consists of beta-blockers, with preference for propranolol or nadolol. Propranolol plasma levels vary greatly among individuals and gastric pH is an important factor for absorption. It is known that propranolol is more stable at acidic pH being the drug decomposed in alkaline solutions.^{Reference Sweetman3} Oral propranolol solution is formulated with 25% citric acid, which likely resulted in better stability and greater bioavailability in our patient with achlorhydria. The authors presume that conversion from oral solution to tablets may have comprised propranolol stability, leading to a reduced bioavailability which likely contributed to the genesis of the arrhythmic storm.

In the case of beta-blocker refractory arrhythmias, thoracic sympathectomy and partial ablation of the stellate ganglion has been shown as an option with promising results in the prevention of arrhythmic recurrences in patients with long QT syndrome.^{Reference Al-Khatib Sana, Stevenson William, Ackerman Michael and Bryant William4} In our patient, although we were concerned that the conversion from propranolol solution to tablets may have contributed to the electrical storm, given the life-threatening nature of the patient’s presentation, in addition to converting back to treatment with propranolol solution, we elected to proceed with surgical sympathectomy. While this combined approach was clinically effective, we were unable to determine whether the transition back to propranolol solution or the sympathectomy were most causal in obtaining arrhythmia control.

In conclusion, this case illustrates the complexity of Jervell-Lange-Nielsen syndrome with regard to how changes in drug formulations that can modify bioavailability must be performed with extreme caution. For such patients, given the risk of life-threatening arrhythmias, clinicians should consider hospitalising patients for continuous heart rhythm monitoring when changes in drug formulation are planned.