Atrial septal defect in a patient with congenital disorder of glycosylation type 1a: a case report

Abstract

BackgroundAtrial septal defect often become more severe when encountered in genetic syndromes. Congenital disorder of glycosylation type 1a is an inherited metabolic disorder associated with mutations in PMM2 gene and can affect almost all organs. Cardiac abnormalities vary greatly in congenital disorder of glycosylation type 1a and congenital heart defects have already been reported, but there is little knowledge about the effect of this inherited disorder on an existing congenital heart defect. Herein we report for the first time on a baby with congenital disorder of glycosylation type 1a with atrial septal defect and make a comparison of changes in atrial septal defect by follow-ups to the age of 3.Case presentationOur patient was an 8-month-old Han Chinese boy. At the initial visit, he presented with recurrent lower respiratory infection, heart murmur, psychomotor retardation, inverted nipples, and cerebellar atrophy. Echocardiography revealed a 8 mm secundum atrial septal defect with left-to-right shunt (Qp/Qs ratio 1.6). Enzyme testing of phosphomannomutase 2 demonstrated decreased levels of phosphomannomutase 2 activities in fibroblasts. Whole exon sequencing showed he was heterozygous for a frameshift mutation (p.I153X) and a missense mutation (p.I132T) in PMM2 gene. The diagnosis of congenital disorder of glycosylation type 1a with atrial septal defect was issued. Now, he is 3-years old at the time of this writing, with the development of congenital disorder of glycosylation type 1a (cerebellar atrophy become more severe and the symptom of nystagmus emerged), the size of atrial septal defect increased to 10 mm and the Qp/Qs ratio increased to 1.9, which suggested exacerbation of the atrial septal defect. Congenital heart defect-associated gene sequencing is then performed and shows there are no pathogenic mutations, which suggested intrinsic cardiac factors are not the cause of exacerbation of the atrial septal defect in our patient and it is reasonable to assume congenital disorder of glycosylation type 1a can worsen the situation of the existing atrial septal defect.ConclusionsThis report highlights the view that congenital disorders of glycosylation type 1a should be excluded when faced with congenital heart defect with cerebellar atrophy or neurodevelopmental delay, especially when the situation of congenital heart defect becomes more and more severe.

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach

“…Our study confirmed previously reported infection-related features in PMM2-CDG, namely (1) the higher prevalence of infections during infancy/early childhood; (2) their organ-specific pattern (particularly RT and GI); (3) the not negligible occurrence of sepsis evolving from organ-specific infections and iv) their associated early lethality [13,14,16,17,52,53]. All these observations highlight the need for close monitoring until full remission occurs to ensure recovery and to prevent clinical aggravation and fatal outcomes [17].…”

Atrial septal defect presenting as intractable congestive heart failure in an infant with dismal outcome: A Case report

“…There are reports showing ASD as very severe when associated with genetic syndromes. Wu et al presented a case of 10 mm ASD in an 8 month-old male infant with congenital disorder of glycosylation [8]. In our patient, there was no dysmorphism or features suggestive of any inborn error of metabolism.…”

Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature

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