Diagnosis and nosology of glycanosis CDG ("carbohydrate deficient glycoprotein syndrome")]

BACKGROUND: The "Carbohydrate-deficient glycoprotein syndrome" is a recently discovered inborn error of complex carbohydrate metabolism. The disease involves a number of organ systems and various deficient glycoproteins. An abnormal isoform of serum transferrin is of diagnostic value. METHODS: We analysed the glycoprotein alpha-1-antitrypsin of two affected infants and their clinically healthy parents using high resolution isoelectric focusing technique. Besides normal isoforms of alpha-1-antitrypsin, we found an abnormal cathodic isoform ("CDG-alpha-1-antitrypsin") which represented almost half of the total amount of alpha-1-antitrypsin of the patients. RESULTS: This new marker-glycoprotein suggests a defect of the production of biantennary and of triantennary N-glycans during an early step of their synthesis, resulting in monoantennary N-glycans. Also this marker-glycoprotein seems to be a specific biochemical diagnostic tool for discovering glycanosis CDG (Carbohydrate-deficient glycoprotein syndrome). The mode of inheritance is probably incomplete autosomal dominant. The same genetic defect of N-glycan synthesis may be present in more than one type of the hybrid molecule glycoprotein, and was also found in transferrin, resembling a "genetic back-pack", that might explain the multitude of clinical symptoms. CONCLUSION: In view of these findings, we present novel systematics of those diseases that are due to inborn errors of N-glycan synthesis, and which we suggest to call "glycanoses".