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Annual Meeting of the North American Society for Pediatric Gastroenterology and Nutrition; Orlando, October 22-24, 1998


Freeze, H*; Srikrishna, G*; Kim, S*; Mehta, D*; Dryhurst, K; Murch, S

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Journal of Pediatric Gastroenterology & Nutrition: October 1998 - Volume 27 - Issue 4 - p 475
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Abstract 49

Mucosal inflammation can cause protein-losing enteropathy (PLE) and loss of epithelial glycosaminoglycans (GAGs) (1). PLE rarely occurs in a normal mucosa, but this was seen in three infants showing a congenital deficiency of enterocyte GAGs (2). The molecular basis is unknown. Most patients with Carbohydrate Deficient Glycoprotein Syndrome (CDGS) Type 1a have severe neurological and developmental delays due to a loss of phosphomannomutase (PMM). Recently, a patient with severe PLE and normal neurological development was diagnosed with CDGS Type 1b (3), resulting from a deficiency in phosphomannose isomerase (PMI). Both Type 1a and 1b lead to underglycosylation of multiple proteins. We now report on a child with life-threatening PLE and enterocyte GAG deficiency that results from another biosynthetic defect in N-linked sugar chain biosynthesis.

At age 3 months, the patient presented with profound PLE following gastroenteritis. Developmental regression has appeared recently. Analysis of serum transferrin, the key indicator protein for CDGS, suggested an absence of entire sugar chains in some molecules, but PMI and PMM were normal.

Metabolic labeling of patient fibroblasts with [2-3H]mannose showed synthesis and accumulation of a truncated, non-glucosylated, lipid-linked oligosaccharide precursor, Man9GlcNAc2-P-P-Dol, which is known to be transferred to proteins less efficiently than that of normal glucosylated precursor, Glc3Man9GlcNAc2-P-P-Dol. This finding could cause underglycosylation of key membrane or matrix glycoproteins required for normal enterocyte GAG accumulation. These results confirm the link between CDGS and PLE and offer an explanation for enterocyte GAG deficiency. It also underscores the need for transferrin testing of all affected infants. (Supported by GM-55695).


(1) Murch et al., Lancet 1993;341:711-4
(2) Murch et al., Lancet 1996;347:1299-1301
(3) Niehues et al., J Clin Invest, 1998;101:1414-1420

Section Description


Transport/Cell Biology/Nutrition

© 1998 Lippincott Williams & Wilkins, Inc.