ESPE Abstracts

Background: Triple A (Allgrove syndrome) is a rare, autosomal recessive disorder characterized by the alacrimia, achalasia, and adrenal insufficiency triad. Alacrimia starts in early infancy, while achalasia and adrenal insufficiency appear subsequently during childhood or adulthood. We are presenting an infant with very early and simultaneous clinical manifestations of triple A syndrome.

Case presentation: An 11-month-old male infant was admitted to the neurological department for evaluation of muscle hypotonia and developmental delay. Mother reported child limpness, feeding problems, and failure to thrive since 6 months of age. Before admission, child had daily fevers for two months due to repeated pneumonia. On admission, clinical examination showed a failure to thrive (weight 6040 g – Z score ˂ -3SD), pale skin with hyperpigmentation in the lumbar region, and abdominal distension without organomegaly. Neurological examination revealed generalized muscle weakness with reduced spontaneous motor activity. He cried without tears since birth. Baseline investigations revealed normal complete blood count, serum creatinine, and salt wasting (serum Na 125 mmol/l, K 6.2 mmol/l, urine Na 30 mmol/L). Based on clinical presentation, and initial laboratory results, neurologist suspected Allgrove syndrome, and referred the patient to the endocrinology department. ACTH concentration was 886 pg/ml, with basal serum cortisol of 165 nmol/l, which failed to increase during the Synachten test (in 30 and 60 minutes cortisol levels were 157 and 159 nmol/l, respectively), while 17-OHP was low throughout the test. Diagnosis of primary adrenal insufficiency was established, and hydrocortisone and fludrocortisone therapy were initiated. Ophthalmic evaluation revealed reduced tear production and local therapy with artificial tears was introduced. Due to swallowing difficulties and repeated vomiting, barium study was performed, and severe stenosis of the lower esophageal sphincter, as well as dilatation of the upper esophagus, were revealed. A diagnosis of achalasia was made and later managed with esophagomyotomy. Molecular genetic testing conducted at the Dresden University of Technology confirmed a compound heterozygous mutation in the AAAS gene: p.Ser263Pro (paternal mutation) and c.787T>C (maternal mutation).

Conclusion: Given the rarity and high phenotypic heterogeneity, early identification of the Triple A syndrome is challenging. According to the current state of literature, the mean age of onset of the first symptom is between 2 and 13 years. Our patient was 6 months old when the triad of signs presented, making him the youngest child with Allgrove syndrome reported so far.