Peroral Endoscopic Myotomy Followed by Antireflux Mucosectomy for Gastroesophageal Reflux in Identical Twins with Allgrove Syndrome

Introduction

Allgrove syndrome (triple A syndrome) is a rare autosomal recessive disorder with a prevalence as low as 1/10,00,000 individuals and presents with a clinical triad of achalasia, alacrimia, and adrenal insufficiency, seen in about 70% of cases. 1,2 The disease has no known cure, and treatment relies on managing symptoms. Peroral endoscopic myotomy (POEM) is a novel clinical technique developed in Japan and used to treat oesophageal achalasia and oesophageal motility disorders. 3 Although there are limited data, POEM in children has shown encouraging success rates and, with further studies, may become the mainstay of paediatric achalasia treatment. 3 This is an unusual case of undiagnosed triple A syndrome with a notable gap between initial symptoms and diagnosis, treated with paediatric POEM, which resulted in the development of gastroesophageal reflux needing antireflux mucosectomy (ARMS).

Case Report

A 13-year-old female born to a consanguineous marriage presented with complaints of progressive dysphagia to solids and liquids, occasional vomiting, nasal regurgitation, and weight loss of ~10 kg over two years (body mass index [BMI] 15 kg/m 2), aggravated in the last four months (Eckardt Symptom Score [ESS] 7). On general examination, she had pallor and hyperpigmented knuckles, with stable vital signs.

Barium swallow showed a “bird-beak” appearance of the oesophagus. Manometry showed oesophageal aperistalsis with an elevated integrated relaxation pressure (IRP) of 21 mmHg, suggesting type I achalasia cardia. An upper endoscopy revealed a dilated oesophagus with liquid residue and resistance while passing the scope across the gastroesophageal junction (GEJ). Her computed tomography (CT) abdomen was unremarkable. She had a history of dry eye symptoms since birth; Schirmer’s test was positive for alacrimia. There was no peripheral neuropathy, and an X-ray of the feet did not show osteoporotic changes. Serum cortisol levels were low, with elevated adrenocorticotropic hormone (ACTH) levels. The diagnosis was triple A (AAA) syndrome.

As per detailed family history, she had an identical twin sister who had similar symptoms of dyspepsia, nasal regurgitation, and weight loss (ESS 6). She also reported a history of alacrimia since childhood and had hyperpigmented knuckles, elbows, ankles, and knees. Her barium swallow, was suggestive of achalasia cardia. Her oesophageal manometry showed failed peristalsis in all swallows with pan-oesophageal pressurisation in > 20% and an elevated median IRP of 23 mmHg. Her adrenal function was normal, while Schirmer’s test was positive. Neither had any signs of neurological involvement. Another sibling, a 16-year-old male, was apparently healthy and without any such symptoms.

The identical twins underwent posterior POEM for achalasia, which involved adequate submucosal tunnelling, posterior myotomy with a 2 cm gastric myotomy, and closure of the mucosal incision with haemoclips (Medorah, India). Both procedures were uneventful. Post-operatively, they were discharged on Day 2 on a liquid diet and transitioned to a soft diet.

Adrenal insufficiency was treated with oral hydrocortisone (Hisone 5 mg) once daily in the first sibling. After a month, both had an ESS of 2, and endoscopy showed a lax lower oesophageal sphincter, allowing easy scope passage. The first child had Grade C oesophagitis, and the second had Grade A oesophagitis. Proton pump inhibitors (PPIs) were prescribed to both; however, the former developed PPI-dependent gastroesophageal reflux disease (GERD). After 6 months post-POEM, the first child underwent ARMS. A 270-degree mucosal resection was performed with cap endoscopic mucosal resection (EMR) after submucosal injection along the cardia. The procedure was uneventful, and the patient was discharged on Day 2. After one month, there was improvement in symptoms and PPIs were stopped. Endoscopy showed no reflux oesophagitis, with a GEJ flap valve and scope grip sign.

Discussion

We present a rare scenario of twins with triple A syndrome who successfully underwent POEM for achalasia. Given its rarity, the long-term outcomes of POEM among the paediatric population are not well described. 3-6 Both patients showed improvement in symptoms of achalasia. We encountered PPI-dependent GERD in one of the patients who was on steroids for adrenal insufficiency. ARMS was performed and showed a good, durable response. Other options to be considered in young patients with achalasia include concomitant fundoplication (POEM-F) or laparoscopic Heller myotomy (LHM) with Dor fundoplication. We offered POEM as primary treatment and performed an antireflux procedure only in the severely symptomatic patient. This case report highlights the usefulness of third-space endoscopy (TSE) in the paediatric population, along with the safety and efficacy of ARMS post-POEM. To our knowledge, there are limited data on such therapeutic options in the paediatric population.

Patients presenting with triple A syndrome often have abnormal or borderline adrenal function, but only a few develop adrenal insufficiency. 4 There are no specific guidelines for surveillance, but these may need lifelong follow-up based on clinical symptoms. Genetic studies were not conducted in our patients, and the diagnosis was based on the classical triad of symptoms. Allgrove syndrome is a very rare condition, with limited mention of POEM for achalasia.7,8 Children presenting with failure to thrive and dysphagia should be evaluated for achalasia. POEM can be offered as a primary treatment modality. We also demonstrated good safety and efficacy of ARMS post-POEM in the paediatric population.

Declarations

Funding: None.

Conflict of Interest: None.

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