Michael Weinstein1,2, E Schollen3, Gert Matthijs3, Christine Neupert4, Thierry Hennet5, Claudia E. Grubenmann5, Christian Frank4, Markus Aebi4, Joe T.R. Clarke1,2, Anne M. Griffiths1,2, L E Seargeant6, Nicola Poplawski1
1Hospital for Sick Children, Pediatrics, Toronto, Ontario, Canada
2University of Toronto, Toronto, Ontario, Canada
3University of Leuven, Center for Human Genetics, Leuven, Belgium
4Swiss Institute of Technology, Institute of Microbiology, Zurich, Switzerland
5Institute of Physiology, University of Zurich, Zurich, Switzerland
6Children's Hospital and University of Manitoba, Winnipeg, Manitoba, Canada
Tóm tắt
AbstractWe describe the second case of congenital disorder of glycosylation type IL (CDG‐IL) caused by deficiency of the ALG9 a1,2 mannosyltransferase enzyme. The female infant's features included psychomotor retardation, seizures, hypotonia, diffuse brain atrophy with delayed myelination, failure to thrive, pericardial effusion, cystic renal disease, hepatosplenomegaly, esotropia, and inverted nipples. Lipodystrophy and dysmorphic facial features were absent. Magnetic resonance imaging of the brain showed volume loss in the cerebral hemispheres and cerebellum and delayed myelination. Laboratory investigations revealed low levels of multiple serum proteins including antithrombin III, factor XI, and cholesterol. Hypoglycosylation was confirmed by the typical CDG type 1 pattern of serum transferrin analyzed by isoelectric focusing. A defect in the ALG9 enzyme was suggested by the accumulation of the DolPP‐GlcNAc2Man6 and DolPP‐GlcNAc2Man8 in the patient's fibroblasts and confirmed by mutation analysis: the patient is homozygous for theALG9mutation p.Y286C. The causal effect of the mutation was shown by complementation assays in alg9 deficient yeast cells. The child described here further delineates the clinical spectrum of CDG‐IL and confirms the significant clinical overlap amongst CDG subtypes. © 2005 Wiley‐Liss, Inc.
