Evidence of GMPPA founder mutation in indigenous Guatemalan population associated with alacrima, achalasia, and mental retardation syndrome

Document Type

Journal Article

Publication Date



American Journal of Medical Genetics, Part A








AAMR; Alacrima achalasia and mental retardation syndrome; congenital disorder of glycosylation; founder mutation; GMPPA


© 2020 Wiley Periodicals, Inc. Congenital disorders of glycosylation (CDG) are a heterogeneous group of inborn errors of metabolism mostly causing multisystem disease. In 2013, biallelic mutations in the GMPPA gene were described in association with one such CDG known as alacrima, achalasia, and mental retardation syndrome (AAMR). To date, 18 patients have been reported, nearly all displaying the same pathognomonic triad of symptoms described in the name. This condition shares considerable phenotypic overlap with Triple-A syndrome caused by biallelic mutations in the AAAS gene; however, AAMR lacks the characteristic adrenocortical findings associated with Triple-A syndrome. We report three patients from two unrelated families with the same homozygous GMPPA mutation (c.265dup, p.L89fs). Notably, both families reported indigenous Maya-Mam heritage and originated from the town of Concepción Chiquirichapa in Quezaltenango, Guatemala. Our cases help to expand the AAMR phenotype by outlining dysmorphic features not well described in the prior cases. Additionally, we encourage all providers with patients presenting with this unique triad of symptoms to consider sequencing of the GMPPA gene. Special consideration should be given to families of Guatemalan Maya-Mam ancestry who may also have this identified founder mutation. Finally, this condition may indeed be underdiagnosed based on a review of the literature.

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