Pericardial and abdominal fluid accumulation in congenital disorder of glycosylation type Ia.
The association of fetal hydrops with Congenital Disorders of Glycosylation (CDG) has been reported previously. Pericardial fluid accumulation and ascites were also observed in a few young patients with CDG type Ia. Here we describe the clinical and biochemical features in three children developing life-threatening extravascular fluid accumulation. All patients carried severe PMM2 mutations comparable to the earlier reported patients with fetal hydrops. One patient was successfully treated with a pericardial-pleural shunt placement. Pericardial fluid accumulation and generalized oedema resolved temporarily in the other two children on regular albumin infusions and the use of diuretics. Sequential abdominal punctures were unsuccessful in the treatment of the extensive ascites production. The use of non-steroid anti-inflammatory agents and the application of high dose steroids had no clinical effect. Severe extravascular fluid accumulation progressed to decompensation and death. Biochemical investigations of the abdominal fluid and pericardial fluid demonstrated a high extracellular protein concentration, increased cytokine concentrations and an abnormal transferrin isoelectric focusing pattern characteristic of CDG type I. Our results are consistent with a local activation of the cytokine pathways and subsequent protein transport through the endothelial surface to the extravascular space. Normal glycosylation of cell surface proteins is essential for the normal fluid balance and protein transport through the pericardial and peritoneal membrane. Future therapeutic efforts should be directed to inhibit the abnormal immune response and excessive protein transport in this life-threatening complication of CDG syndrome.
Department of Pediatrics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Gerben
G
Truin
Laboratory of Pediatrics and Neurology, Radboud University, Nijmegen, The Netherlands.
Mailys
M
Guillard
Laboratory of Pediatrics and Neurology, Radboud University, Nijmegen, The Netherlands.
Dirk J
DJ
Lefeber
Department of Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland.
Jolanta
J
Sykut-Cegielska
Department of Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland.
Maciej
M
Adamowicz
Department of Pediatrics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Esther
E
Hoppenreijs
Department of Pediatrics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Rob C A
RCA
Sengers
Laboratory of Pediatrics and Neurology, Radboud University, Nijmegen, The Netherlands.
Ron A
RA
Wevers
Department of Pediatrics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Eva
E
Morava
D001202:Ascitic Fluid / Q000737:chemistry / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D017809:Fatal Outcome; D005260:Female; D006031:Glycosylation; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010490:Pericardial Effusion / Q000378:metabolism* / Q000628:therapy; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
D016207:Cytokines; D014168:Transferrin; D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human