A rare cause of infantile achalasia: GMPPA-congenital disorder of glycosylation with two novel compound heterozygous variants

Am J Med Genet A. 2022 Aug;188(8):2438-2442. doi: 10.1002/ajmg.a.62859. Epub 2022 Jun 4.

Abstract

Achalasia is rare in the pediatric population and should prompt clinicians to consider genetic disorders associated with this condition. While AAA syndrome (also known as Allgrove or Triple A syndrome) is commonly considered, GMPPA-congenital disorder of glycosylation (CDG) should also be in the differential diagnosis. We report a 9-month-old female born to nonconsanguineous parents with achalasia and alacrima found to have two novel compound heterozygous variants in the GMPPA gene associated with GMPPA-CDG. This rare disorder is commonly associated with developmental delay and intellectual disability. We discuss management of this disorder including the importance of confirming a genetic diagnosis and summarize reported cases.

Keywords: AAMR; GMPPA; achalasia; congenital disorder of glycosylation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenal Insufficiency* / genetics
  • Child
  • Congenital Disorders of Glycosylation* / complications
  • Congenital Disorders of Glycosylation* / diagnosis
  • Congenital Disorders of Glycosylation* / genetics
  • Esophageal Achalasia* / diagnosis
  • Esophageal Achalasia* / genetics
  • Eye Diseases, Hereditary* / genetics
  • Female
  • Glycosylation
  • Humans
  • Infant

Supplementary concepts

  • Achalasia Addisonianism Alacrimia syndrome