Lectin analyses of glycoprotein hormones in patients with congenital disorders of glycosylation.

Abstract

OBJECTIVE:

The congenital disorders of glycosylation (CDGs) are progressive multisystemic disorders characterized by a heterogeneous deficiency of the carbohydrate moieties in various structural and circulating glycoproteins, representing a natural model for glycoprotein hormone studies. Here, we studied the carbohydrate moiety of circulating glycoprotein hormones in four patients with a clinical suspicion of CDGs.

METHODS:

The diagnosis of CDG-I was confirmed in two out of the four cases by transferrin isoelectrofocusing (IEF) and/or carbohydrate-deficient transferrin (CDT) test. The carbohydrate moiety of serum endocrine-related glycoproteins was investigated by means of Ricin (immunopurified thyrotropin (TSH)) and Concanavalin A (Con-A) (TSH, follicle-stimulating hormone, alpha-subunit and thyroglobulin) lectin affinity chromatography measurement.

RESULTS:

CDT concentrations were very high in the two patients with CDG-I and moderately enhanced in the remaining two. In the two CDG-I patients, Ricin analysis of immunopurified TSH showed a severe impairment of lectin binding, both before and after neuroaminidase treatment, indicating a nearly complete lack of terminal sialic acid and galactose residues. In these two cases, Con-A analysis showed a significant prevalence of firmly bound isoforms with poorly processed carbohydrate chains. In the remaining two cases with unknown CDG classification, TSH binding pattern to Ricin was modestly affected and Con-A analysis showed the prevalence of weakly bound glycoprotein isoforms.

CONCLUSIONS:

The results of Ricin analyses in all four patients were consistent with the CDT test and/or serum transferrin IEF. The severe alteration of TSH binding pattern to Ricin seems to be characteristic of CDG-I. Nevertheless, TSH biological properties are not severely altered, as normal thyroid function was found in both cases.

• Authors: M C Ferrari, R Parini, M D Di Rocco, G Radetti, P Beck-Peccoz, L Persani
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 144 Issue 4 Pg. 409-16 (Apr 2001) ISSN: 0804-4643 [Print] England
• PMID: 11275952 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoproteins
• Hormones
• Lectins
• Thyrotropin
• Ricin

Topics

• Carbohydrate Metabolism, Inborn Errors (metabolism)
• Child, Preschool
• Chromatography, Affinity
• Female
• Glycoproteins (analysis)
• Glycosylation
• Hormones (analysis)
• Humans
• Infant
• Lectins
• Male
• Ricin
• Thyrotropin (blood, isolation & purification)