Carbohydrate deficient serum transferrin in a new systemic hereditary syndrome

• Published in: Archives of disease in childhood Vol. 65; no. 1; pp. 107 - 111
• Main Authors: Stibler, H, Jaeken, J
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health 01-01-1990; BMJ; BMJ Publishing Group Ltd; BMJ Publishing Group LTD
• Subjects: Adipose tissue; Affinity chromatography; Anatomy; Anion exchange; Biological and medical sciences; Biomarkers - blood; Bone composition; Carbohydrate composition; Carbohydrate Metabolism, Inborn Errors - blood; Carbohydrate Metabolism, Inborn Errors - genetics; Carbohydrates; Child; Child, Preschool; Chromatography; Complex syndromes; Evaluation; Female; Galactose; Genetic disorders; Glycoproteins; Growth Disorders - blood; Growth Disorders - genetics; Health aspects; Hormones; Humans; Isoelectric Focusing; Isoelectric points; Isoforms; Lipids; Mannose; Medical genetics; Medical sciences; N-Acetylglucosamine; Nervous system; Nervous System Diseases - blood; Nervous System Diseases - genetics; Patients; Pediatric diseases; Pediatrics; Physiological aspects; Syndrome; Syndromes; Syndromes in children; Transferrin; Transferrin - analogs & derivatives; Transferrin - analysis; Transferrins; Human; Nervous system diseases; Transferrin; Isoelectrical focusing; Deficiency; Metabolic diseases; Serum protein; Complex syndrome; Genetic disease
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/adc.65.1.107

Four patients with a new, inherited, complex developmental deficiency syndrome were studied. The syndrome affects the central and peripheral nervous system, and also the retina, liver, bone, adipose tissue, and genital organs. Abnormalities of glycoproteins, glycopeptide hormones, and lipids have been found in serum from these patients, the most pronounced being increased cathodal forms of transferrin. Isoforms of serum transferrin were therefore analysed qualitatively and quantitatively by isoelectric focusing and isocratic anion exchange chromatography, and the carbohydrate composition was determined in transferrin isolated by immune affinity chromatography. All the patients had about tenfold raised serum concentrations of isotransferrins with higher isoelectric points than normal. Similar findings, though less pronounced, were made in all the fathers and in one of the mothers. Half the transferrin in the patients was constantly present in two principal abnormal cathodal forms in approximately equal amounts. Carbohydrate determinations in purified transferrin showed quantitatively similar deficiencies of sialic acid, galactose, and N-acetylglucosamine, the mannose content being normal. The results suggest that either two or all of the normally four terminal trisaccharides in transferrin may be missing. A defect in the synthesis or catabolism, or both, of this trisaccharide, which is common to many secretory glyco-conjugates, is likely. Apart from providing a quantitative diagnostic method, the present findings may serve as a basis for further studies of the metabolic deficiency in this syndrome.