Noelle Vera, Knuepfer Matthias, Pulzer Ferdinand, Schuster Volker, Siekmeyer Werner, Matthijs Gert, Vogtmann Christoph
University Children's Hospital, Oststrasse 21-25, 04317 Leipzig, Germany.
Eur J Pediatr. 2005 Apr;164(4):223-6. doi: 10.1007/s00431-004-1611-x. Epub 2005 Jan 12.
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 PMM2gene 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.
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.
在先天性糖基化障碍（CDG）综合征中，1a型最为常见。CDG 1a是一种具有广泛临床谱的多系统疾病。我们报告了一例患有严重且致命病程的CDG 1a综合征足月儿。皮肤成纤维细胞显示磷酸甘露糖变位酶2（PMM2）活性降低，突变分析揭示了复合杂合性PMM2基因突变（F119L/F157S）。出生时的表现为肥厚性非梗阻性心肌病、“橘皮样”皮肤、乳头内陷以及因明显外周水肿而呈现的水肿样外观。由于缺乏腹水和胸腔积液，疑似胎儿水肿未得到证实。显著的临床问题包括难治性动脉高血压、反复出现的心包和胸腔积液以及喂养困难伴生长发育迟缓。在无感染情况下发现持续性先天性血小板减少症和高铁蛋白血症。骨髓细胞学检查显示病因不明的巨噬细胞活化。
先天性血小板减少症、非特异性巨噬细胞活化以及无真正胎儿水肿的水肿样外观拓宽了先天性糖基化障碍综合征1a型本已广泛的表型谱。
