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

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 st udied 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 trans ferrin (CDT) test. The carbohydrate moiety of serum endocrine-related glyco proteins was investigated by means of Ricin (immunopurified thyrotropin (TS H)) and Concanavalin A (Con-A) (TSH, follicle-stimulating horomone, alpha-s ubunit and thyroglobulin) lectin affinity chromatography measurement. Results: CDT concentrations were very high in the two patients with CDG-I a nd moderately enhanced in the remaining two. In the two CDG-I patients, Ric in analysis of immunopurified TSH showed a severe impairment of Lectin bind ing, both before and after neuroaminidase treatment, indicating a nearly co mplete lack of terminal sialic acid and galactose residues. In these two ca ses, Con-A analysis showed a significant prevalence of firmly bound isoform s with poorly processed carbohydrate chains. In the remaining two cases wit h unknown CDG classification, TSH binding pattern to Ricin was modestly aff ected and Con-A analysis showed the prevalence of weakly bound glycoprotein isoforms. Conclusions: The results of Ricin analyses in all four patients were consis tent with the CDT test and/or serum transferrin IEE The severe alteration o f TSH binding pattern to Ricin seems to be characteristic of CDG-I. Neverth eless, TSH biological properties are not severely altered, as normal thyroi d function was found in both cases.