Unusual presentation of congenital disorder of glycosylationtype 1a: congenital persistent thrombocytopenia, hypertrophic cardiomyopathy and hydrops-like aspect due to marked peripheral oedema

Of the congenital disorder of glycosylation (CDG) syndromes, type 1a is the most common. CDG 1a is a multisystem disorder with a wide clinical spectrum. We report on a term newborn with a severe and fatal clinical course of CDG 1a syndrome. Skin fibroblasts showed a reduced activity of phosphomannomutase 2 (PMM2) and mutation analysis revealed a compound heterozygous PMM2 gene mutation (F119L/F157S). Presenting features at birth were hypertrophic non-obstructive cardiomyopathy, orange-peel skin, inverted nipples and a hydrops-like aspect due to marked peripheral oedema. Suspected hydrops fetalis was not confirmed due to lack of ascites and pleural effusions. Striking clinical problems were therapy-resistant arterial hypertension, recurrent pericardial and pleural effusions and feeding difficulties with failure to thrive. Persistent congenital thrombocytopenia and hyperferritinaemia in the absence of infection were noted. Bone marrow cytology revealed a macrophage activation of unknown aetiology. Conclusion: Congenital thrombocytopenia, unspecific macrophage activation and a hydrops-like aspect without a real hydrops fetalis broaden the already wide phenotypic spectrum of congenital disorder of glycosylation syndrome type 1a.