Federica Gaiani1, Pierpacifico Gismondi2, Roberta Minelli1, Giovanni Casadio3, Nicola de'Angelis4, Fabiola Fornaroli1, Gian Luigi de'Angelis1, Marco Manfredi5. 1. Gastroenterology and Endoscopy Unit, University Hospital of Parma, University of Parma. 2. Pediatric Clinic. 3. Pediatric Surgery, "Pietro Barilla" Children's Hospital, University Hospital of Parma, Parma, Italy. 4. Department of Digestive, Hepatobiliary Surgery and Liver Transplantation, Henri Mondor University Hospital, Créteil, France. 5. Pediatric Unit, Maternal and Child Department, Azienda USL of Reggio Emilia, Sant'Anna Hospital, Castelnovo ne' Monti, Italy.
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.
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.
Authors: Erica L Macke; Joel A Morales-Rosado; Sarah K Macklin-Mantia; Christopher T Schmitz; Björn Oskarsson; Eric W Klee; Klaas J Wierenga Journal: Mol Genet Genomic Med Date: 2022-05-15 Impact factor: 2.473