Case report of a familial triple: a syndrome and review of the literature

Abstract

Rationale: Triple-A syndrome, or Allgrove syndrome (AS), is a rare autosomal recessive disorder characterized by the alacrimia, achalasia, and adrenal insufficiency triad. Alacrimia usually starts at early infancy, while achalasia and adrenal insufficiency appear later during childhood or adulthood. Some patients may also present with the so-called Double-A syndrome (i.e., alacrimia and achalasia, or alacrimia and adrenal insufficiency); adrenal insufficiency usually represents a life-threatening event due to severe hypoglycemia. Many patients may also present other associated manifestations, such as neurological disorders. We describe, here, 2 sisters of non-consanguineous parents. Patient concerns: An 8-year-old girl was admitted to the Pediatric Care Unit of Parma after an episode characterized by seizure with loss of consciousness and generalized hypertonia lasting a few minutes. Her sister, a 6-year-old girl, presented with recurrent episodes of vomiting and failure to thrive. Diagnoses: Both children were investigated by laboratory tests, esophagogastroduodenoscopy, and imaging. The first patient had the complete triad of AS (alacrimia, achalasia, adrenal insufficiency), while the second one presented only alacrimia and achalasia. Both resulted from a mutation in the achalasia, addisonianism, alacrimia syndrome gene. Interventions: Both patients were treated with oral hydrocortisone for Addison disease, and with artificial tears in the first case. After many pneumatic endoscopic dilations and therapy with nifedipine, both patients underwent surgical Heller myotomy for achalasia. Outcomes: A rapid and favorable recovery to normal diet and with improvement of growth parameters was obtained. These cases are also compared with the literature data, reported in a brief review. Lessons: AS is a rare multisystemic disorder. The longer diagnosis is delayed, the greater extent to which this syndrome may be life-threatening, mainly because of hypoglycemia due to adrenal insufficiency. In AS, the red-flag symptom of alacrimia should instigate investigation for achalasia, Addison disease, and achalasia, addisonianism, alacrimia syndrome gene mutation.

Mineralocorticoid Deficiency as an Early Presenting Symptom of Allgrove Syndrome With Novel Mutation: A Case Report

“…Considering the widely phenotypic variability of the presentation, the initial diagnosis is often delayed. Hence, physicians should be vigilant with a high index of suspicion to bridge the significant gap between initial symptoms and the diagnosis [2,3]. As compared to others, our patient has an early age of presentation.…”

“…Owing to the fact that this syndrome is underreported due to missed diagnosis, the exact incidence is still unknown [6]. Although most of the patients present during the latter half of the first decade of their life, adult-age onsets have also been reported [2,5]. Considering the widely phenotypic variability of the presentation, the initial diagnosis is often delayed.…”

“…Allgrove syndrome (AS), also known as triple-A syndrome (achalasia, adrenal insufficiency, and alacrimia (absences of tears)), is a multi-systemic disorder that was first described in 1978 [1]. The spectrum of the disease widely varies, and it can be variably associated with autonomic nervous system dysfunction and called 4-A Syndrome [2].…”

Triple A Multisystem Disorder: Allgrove Syndrome

“…While for achalasia treatment modalities differ with the varying degrees of dysphagia and esophageal patency. Mild to moderate achalasia might be responsive to pneumatic endoscopic esophageal dilation and pharmacotherapy such as nifedipine, while severe achalasia might require esophageal myotomy procedures such as Heller's myotomy [14]. Lastly, adrenal insufficiency is variable between patients and can present as partial adrenal insufficiency (such as our case) or as severe as an adrenal crisis.…”

“…This led to his poor health status upon presentation. Early detection of AS is a crucial aspect of the disease management, and early interventions might minimize the life-threatening complications of adrenal insufficiency [13,14].…”