Two siblings with triple A syndrome

Area of Science:

• Genetics and rare diseases
• Pediatric endocrinology
• Gastroenterology

Background:

• Triple A syndrome (Allgrove syndrome) is a rare autosomal recessive disorder.
• It is characterized by the triad of adrenal insufficiency, achalasia, and alacrima, often with neurological symptoms.

Observation:

• Two siblings from a consanguineous marriage presented with overlapping symptoms of Triple A syndrome.
• Patient 1 developed dysphagia at age 4; Patient 2 showed an abnormal gait at age 2.
• Both siblings exhibited alacrima, achalasia, adrenal insufficiency, and ACTH resistance.

Findings:

• Genetic analysis revealed a homozygous pathogenic variant in the achalasia-adrenal insufficiency-alacrima syndrome gene (AAAS gene).
• The findings confirm the genetic basis of the disorder in the affected siblings.

Implications:

• Early clinical suspicion and investigation of alacrima are vital for timely diagnosis of Triple A syndrome.
• Prompt management can help mitigate potential neurological complications associated with the condition.