Congenital Disorder of Glycosylation IId (CDG-IId) - A New Entity: Clinical Presentation with Dandy-Walker Malformation and Myopathy

V. Peters; J. M. Penzien; G. Reiter; C. Körner; R. Hackler; B. Assmann; J. Fang; J. R. Schaefer; G. F. Hoffmann; P. H. Heidemann

doi:10.1055/s-2002-23597

Neuropediatrics, Table of Contents

Neuropediatrics 2002; 33(1): 27-32
DOI: 10.1055/s-2002-23597

Original Article

Georg Thieme Verlag Stuttgart · New York

Congenital Disorder of Glycosylation IId (CDG-IId) - A New Entity: Clinical Presentation with Dandy-Walker Malformation and Myopathy

V. Peters¹ , J. M. Penzien² , G. Reiter² , C. Körner³ , R. Hackler⁴ , B. Assmann¹ , J. Fang¹ , J. R. Schaefer⁴ , G. F. Hoffmann¹ , P. H. Heidemann²

¹ Universitäts-Kinderklinik, Sektion für Metabolische und Endokrinologische Erkrankungen, Heidelberg, Germany
² Klinikum Augsburg, I. Klinik für Kinder und Jugendliche, Augsburg, Germany
³ Georg-August-Universität Göttingen, Abt. Biochemie II, Göttingen, Germany
⁴ Zentrum für Innere Medizin, Abt. Kardiologie, Baldinger Strasse, Marburg, Germany

Abstract

A 1.5-year-old boy with macrocephaly due to a Dandy-Walker malformation presented with progressive hydrocephalus, extensive muscular hypotonia, transient cholestatic syndrome, extensive coagulation abnormalities and elevated creatine kinase indicating myopathy. Diagnostic work-up indicated a congenital disorder of glycosylation (CDG, formerly carbohydrate deficient glycoprotein syndrome). The serum transferrin pattern obtained by automated isoelectric focusing (IEF) showed an hitherto unreported pattern with strongly elevated tri-, di-, mono- and asialotransferrin bands, increasing in this order together with markedly decreased tetrasialotransferrin. Investigation of two additional glycoproteins, α₁-antitrypsin and α₁-antichymotrypsin, confirmed a generalised defect of glycosylation. All known glycosylation defects could be ruled out by enzymatic analyses in either leukocytes or fibroblasts or by the results obtained by IEF. SDS-electrophoresis demonstrated a marked difference in the molecular weight of transferrin, suggesting the lack of parts or of all oligosaccharide chains. The defect could be delineated to a deficiency of β-1,4-galactosyltransferase (E.C.2.4.1.38) due to a homozygous insertion (1031 - 1032 insC). Details of the biochemical and molecular findings will be described elsewhere.

Key words

Congenital Disorders of Glycosylation - CDG - Isoelectric Focusing - Transferrin - α₁-Antitrypsin - α₁-Antichymotrypsin - Myopathy - Dandy-Walker Malformation

Full Text

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Dr. rer. nat. Verena Peters

Universitäts-Kinderklinik, Sektion für Metabolische und Endokrinologische Erkrankungen

Im Neuenheimer Feld 150

69120 Heidelberg

Germany

Email: Verena_Peters@med.uni-heidelberg.de