J Inherit Metab Dis (2006) 29:592

DOI 10.1007/s10545-006-0275-2

S H O R T R E P O R T

Recurrent infections and immunological dysfunction in congenital

disorder of glycosylation Ia (CDG Ia)

C. Blank · L. A. Smith · D. A. Hammer ·

M. Fehrenbach · H. M. DeLisser · E. Perez ·

K. E. Sullivan

Received: 5 November 2005 / Accepted: 24 May 2006 / Published online: 6 July 2006C SSIEM and Springer 2006

Online citation: JIMD Short Report #012 (2006) Online

Summary Congenital disorder of glycosylation Ia is the

most common defect of glycosylation and is dueto mutations

in phosphomannomutase 2. This leads to aberrant N-linked

oligosaccharides. The phenotype of CDG Ia reflects the

essential nature of glycosylation and patients typically

present with multiple organs affected, with hypotonia,

developmental delay, inverted nipples and abnormal fat

pads. Later features include retinitis pigmentosa, stroke,

cerebellar atrophy and malabsorption. Approximately 20%

of patients die in the first year of life and infection is the most

common cause of death. Immunological function has not

previously been investigated in these patients and the critical

role of oligosaccharides on adhesion molecules suggested

Communicating editor: Jaak Jaeken

C. Blank 

Gettysburg Pediatrics, Gettysburg, Pennsylvania, USA

L. A. Smith

Department of Chemical and Biomolecular Engineering,

University of Pennsylvania, Pennsylvania, USA

D. A. Hammer

Department of Bioengineering, University of Pennsylvania,

Pennsylvania, USA

M. Fehrenbach · H. M. DeLisser

Pulmonary, Allergy and Critical Care Division, Department of 

Medicine, University of Pennsylvania School of Medicine,

Pennsylvania, USA

E. Perez · K. E. Sullivan ()

Department of Pediatrics, Children’s Hospital of Philadelphia,

Pennsylvania, USA

e-mail: sullivak@mail.med.upenn.edu

Electronic Supplementary Material

Supplementary material is available for this article at

http://dx.doi.org/10.1007/s10545-006-0275-2

that haematopoietic cell migration and communication

could be disrupted by mutations in phosphomannomutase 2.

We characterized the clinical features, performed standard

immunological evaluations, and performed specific anal-

yses of neutrophil adhesion molecules on two patients to

address this question. Patient neutrophils had diminished

chemotaxis but expressed comparable levels of adhesion

molecules and rolled on artificial endothelium equivalently

to control neutrophils. The most significant feature of 

the patients’ immunological function was poor vaccine

responses. These two affected patients were begun on in-

travenous immunoglobulin with some improvement in their

infections.

Springer