Is Alacrima So Prevalent in Patients With Early-Onset Achalasia?

Abstract

TO THE EDITOR: Genetic factors have been suggested to play an important role in development of achalasia, and various candidate genes have been documented.1 ALADIN is one of candidate genes. However, study by Di Nardo et al2 has shown that no pathogenic mutations were detected in ALADIN gene of 41 patients with isolated achalasia. In addition, Allgrove syndrome is a rare disorder, and achalasia is usually present in infancy, despite of one case report with adult-onset disease.1,3 The study by Jung et al4 itself was very well-designed and well-organized to investigate genetic predisposition as cause of achalasia. The authors tried to selectively enroll patients with early-onset disease and accompanying alacrimia in order to increase possibility of detecting genetic abnormality in ALADIN gene. This contrasted design of study by Di Nardo et al2 in which analyzed patients with a wider range of age.4 After they opened Aladdin's magic lamp, however Jung and his colleagues found that the genie in lamp did not exist, despite of their appropriate plan and great effort. In other words, no mutations were detected in genes of selected patients with early-onset disease and accompanying alacrimia. Herein, I have 2 trivial points to discuss with Jung and his colleagues. They reported that prevalence of alacrima is as high as 42% in patients with early-onset achalasia.4 In their study, cut-off value for alacrima was defined as 10 mm/5 min with Schirmer I test (without anesthesia) according to reference.4,5 However, cited reference showed that recommended cut-off value for dry eye with Schirmer I test is 5 mm/5 min.5 Therefore, study by Jung et al4 might overestimate prevalence of alacrima using, without documented reason, a cut-off value higher than one recommended in cited test. Instead I consider that authors should estimate prevalence by using recommended cut-off value of 5 mm/5 min. Additionally, in study by Verma et al,6 Schirmer test was performed with anesthesia with 5 mm/5 min cut-off value of alacrimia. Therefore, I consider that 20% prevalence of alacrimia reported in study of Verma et al6 should not be directly compared with findings from study of Jung et al.4 Nevertheless, Jung et al4 have established an excellent cohort of early-onset achalasia, and I expect them to detect novel genetic factors, should they decide to continue investigation of genes responsible for development of achalasia, different from ALADIN gene.