ESPE Abstracts

Background: Allgrove syndrome (AS) is a rare autosomal recessive disease characterized by alacrimia, achalasia, adrenal insufficiency and variable autonomic, central or peripheral nervous system dysfunction due to (AAAS) gene mutation on 12q13 coding ALADIN protein. Simultaneous onset of all clinical features is not a rule. Alacrimia is the earliest and constant symptom presenting since birth. However, achalasia is the most common complaint bringing children to physicians whereas hypoglycemia secondary to adrenal insufficiency is a life threatening event and the second complaint leading to severe morbidity and mortality.

Case: A 3-year-old-male, without parental consanguinity, presented after 12 hours of coma associated with generalized tonic-clonic seizures. His past medical history revealed alacrimia since birth followed by post-prandial vomiting at 6 months of age which was investigated by barium swallow manometry and diagnosed as achalasia. His physical exam showed neck, abdominal and inguino-scrotal hyperpigmentation with weight: 11 kg <5^th percentile, height: 89cm <10^th percentile, BMI: 13.85 Kg/m². He presented with many fainting attacks. Laboratory studies showed glycemia: 31 mg/dl, Na: 135mEq/dl, K: 5mEq/dl, cortisol: 0µg/dl, ACTH: 1313pg/ml. It was a missed AS or triple A syndrome diagnosis. A complete resuscitation with fluids, glucose, gluco-corticoids, and anti-epileptic was done but he passed away.

Discussion: Allgrove described two pairs of siblings in 1978. Alacrimia is the earliest feature (90%) and should be as a red flag for pediatricians, confirmed by Schirmer test<5mm in 5 minutes and treated by artificial tears. Achalasia (75%) manifesting by vomiting, dysphagia, weight loss, cough, aspiration, confirmed by barium swallow (bird-beak), endoscopy, manometry and treated by pneumatic dilatation, nifedipine, or Heller myotomy. Adrenal insufficiency (75%) presents by hyper-pigmentation, hypoglycemia or hypotensive attacks leading to high morbidity or mortality and treated by hydrocortisone and rarely affecting the mineralo-corticoid activity (15%). Neurologic dysfunction involving the central, peripheral or autonomic nervous system is often associated with AS and called 4A syndrome. There is a significant gap between initial symptoms and diagnosis. Our case was typical but was neither recognized nor treated.

Conclusion: As is an under-diagnosed disorder and delayed diagnosis leads to a life threatening condition due to hypoglycemia secondary to adrenal failure causing a high risk of morbidity and mortality. A high index of suspicion is needed when any child presents with alacrimia followed by vomiting, dysphagia, hyper-pigmentation and hypoglycemia. Our role is to familiarize general pediatricians and teach them about this rare multi-systemic disease which needs multidisciplinary approach including ophthalmologists, gastroenterologists, endocrinologists, surgeons and neurologists.