We investigated the metabolic defect(s) of four children who presented with isolated cryptogenic chronic
liver disease, coagulopathy, and abnormalities of several unrelated serum
glycoproteins. Analysis of the patients' serum
glycoproteins and fibroblasts suggest they have a novel
congenital disorder of glycosylation (CDG). All had abnormal
transferrin (Tf) isoelectric focusing (IEF) profiles. More detailed analysis of Tf by electrospray ionization mass spectrometry (ESI-MS) showed a plethora of abnormal glycosylations that included loss of 1-2
sialic acids and 1-2
galactose units, typical of Group II defects. Tf from two patients also lacked 1-2 entire
oligosaccharide chains, typical of Group One disorders. Total serum N-
glycans were analyzed by HPLC and matrix-assisted
laser desorption/ionization mass spectrometry and also showed increased proportion of neutral
glycan chains lacking
sialic acids and
galactose units. Analysis of patient fibroblasts eliminated CDG-Ia, through CDG-Ih, -IL and
CDG-IId. Our results suggest that a subset of children with clinically asymptomatic, cryptogenic hypertransaminasemia and/or liver steato-
fibrosis may represent a novel type of CDG-X with an unknown defect(s). Clinicians are encouraged to test such patients for abnormal Tf glycosylation by ESI-MS.