POEM in Allgrove syndrome shows earlier symptom onset and favorable outcomes versus idiopathic achalasia

BackgroundAllgrove syndrome is a rare autosomal recessive disorder characterized by the triad of alacrima, adrenal insufficiency, and achalasia. Although corticosteroid replacement and artificial tears effectively manage adrenal insufficiency and alacrima, the optimal treatment for achalasia in this syndrome remains challenging and poorly defined.MethodsAll patients diagnosed with Allgrove syndrome were identified between 2009 and 2025 at Peking Union Medical College Hospital, which is a national rare disease center in China. Clinical characteristics and genetic mutations were collected and analyzed, and the long-term safety and efficacy of peroral endoscopic myotomy (POEM) in Allgrove syndrome were evaluated through follow-up telephone interviews. A comparison cohort of idiopathic achalasia (IAC) patients undergoing POEM, matched for follow-up duration, was enrolled to delineate disease-specific features.ResultsSeven patients were diagnosed with Allgrove syndrome at our institution over the past 16 years, and all of them had homozygous or compound heterozygous mutations in the AAAS gene. The patients presented with alacrima from infancy developed adrenal insufficiency during childhood and were diagnosed with Allgrove syndrome at a mean age of 17. Compared to 12 matched idiopathic achalasia patients, Allgrove patients exhibited a significantly earlier onset of achalasia symptoms (mean age: 12.5 vs. 33.8 years, p = 0.004), with similar intervals from symptom onset to intervention. Interestingly, despite comparable objective severity based on manometric and endoscopic assessments, Allgrove patients reported significantly lower subjective symptom scores (Eckardt score 5.3 vs. 7.6, p = 0.046). Over a median follow-up of 5.8 years, the mean Eckardt score decreased from 5.3 to 0.8 in Allgrove patients and from 7.6 to 1.9 in idiopathic achalasia patients at the last follow-up.ConclusionAllgrove syndrome should be taken into consideration in patients with early-onset achalasia. POEM provides effective and sustained symptom relief for achalasia in Allgrove syndrome, with a favorable safety profile.