Hemolytic Uremic Syndrome Attributable to Streptococcus pneumoniae Infection: A Novel Cause for Secondary Protein N-Glycan Abnormalities

Abstract

Hypoglycosylation of glycoproteins is characteristic for congenital disorders of glycosylation (CDG) and may consist of partial or completely missing glycans (1). The major first test for CDG is isoelectric focusing (IEF) of plasma transferrin. The IEF pattern shows a cathodal shift because of the hypoglycosylation of the protein (2). Primary defects in the N-glycan biosynthetic pathway are known for nine CDG subtypes: CDG Ia–f and CDG IIa–c (3)(4)(5)(6)(7)(8). Transferrin hypoglycosylation can also be secondary to chronic alcohol abuse (9)(10), galactosemia (11), hereditary fructose intolerance (12), and severe liver pathology (9). In this report we describe the association of a transient abnormal transferrin N-glycosylation pattern in plasma and the clinical forms of hemolytic uremic syndrome (HUS) (13)(14)(15) associated with a Streptococcus pneumoniae infection (16). Five patients with HUS associated with a S. pneumoniae infection (age range, 9 months to 2 years) were studied. They fulfilled the criteria for HUS [hemolytic anemia with microangiopathic changes on peripheral blood smear (Burr cells), acute renal failure, and thrombocytopenia] and presented with pneumonia or meningitis. S. pneumoniae was isolated from body fluids of the five patients. We also studied three patients with HUS attributable to verocytotoxin-producing Escherichia coli (VTEC) infection and one case of familial HUS of unknown etiology. von Willebrand factor cleaving protease deficiency and a defect in factor H were excluded in this patient. The sialotransferrin fractions for the five S. pneumoniae -associated HUS cases and healthy controls are shown in Table 1⇓ and Fig. 1⇓ . In healthy individuals (Fig. 1A⇓ , lane 1), the major transferrin form is the tetrasialo form. In all HUS cases associated with S. pneumoniae , the tetrasialotransferrin fraction was markedly decreased and the a-, mono-, and …