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1.
Am J Med Genet A ; 182(3): 425-430, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898852

RESUMO

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.


Assuntos
Insuficiência Adrenal/genética , Acalasia Esofágica/genética , Glicosilação , Deficiência Intelectual/genética , Nucleotidiltransferases/genética , Adolescente , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/patologia , Criança , Consanguinidade , Acalasia Esofágica/epidemiologia , Acalasia Esofágica/patologia , Éxons/genética , Feminino , Homozigoto , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/patologia , Masculino , Mutação/genética , Proteínas do Tecido Nervoso/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Linhagem , Fenótipo
2.
Mol Syndromol ; 9(2): 110-114, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29593478

RESUMO

The alacrima, achalasia, and mental retardation syndrome (AAMR) is a newly described autosomal recessive disorder characterized by the onset of these 3 main features at birth or in early infancy. At present, only 16 cases have been reported. Recently, it was shown that AAMR is due to mutations in the guanosine diphosphate (GDP)-mannose pyrophosphorylase A (GMPPA) gene. These mutations induce a significant GDP-mannose overload, which may affect protein glycosylation. Herein, for the first time, we describe 2 adult sisters with AAMR with a previously not reported deleterious homozygous missense mutation c.1118G>C (p.Arg373Pro) in the GMPPA gene, born to healthy consanguineous heterozygous parents from an ancient endogamous population. The main symptoms in both sisters started soon after birth with achalasia and feeding difficulties, requiring surgical treatment. Both sisters showed alacrima identified during the first months of life, delayed psychomotor development, speech delay, facial dysmorphism, limb defects, short stature, and moderate intellectual disability. Alacrima and feeding difficulties due to achalasia during the neonatal period or first months of life, in the absence of adrenal cortical insufficiency, should spur to investigate AAMR by sequencing the GMPPA gene.

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