Pediatric Protein-Losing Enteropathy Differential Diagnoses

Updated: Jul 25, 2017
  • Author: Simon S Rabinowitz, MD, PhD, FAAP; Chief Editor: Carmen Cuffari, MD  more...
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Diagnostic Considerations

Protein-losing enteropathy (PLE) is a symptom related to a diverse group of disorders (see Causes). With the increased identification of syndromes in the neonatal period and infancy, numerous discrete entities can now be considered when PLE presents in the first year of life. 

Alpha-1,3-glucosyltransferase has been described in 89 patients making it one of the most common forms of congenital disorders of glycosylation. All patients have developmental delay and hypotonia. [35] Epilepsy, ataxia, proximal muscle weakness, failure to thrive, intractable seizures, coagulation anomalies, and autistic spectrum features are frequently noted. Affected children exhibiting PLE often die in the first decade of life.

A child with severe skeletal dysplasia, thanatophoric dysplasia type I, died due to severe PLE by age 6 months, secondary to lymphangiectasia in the small intestine. [36]

DGAT-1, an inborn error of lipid metabolism that is associated with severe diarrhea and hypoalbuminemia, was found to be the cause of PLE in 3 additional children from 2 families with early onset of symptoms. [37]

A case of neonatal diabetes with pancreatic hypoplasia due to GATA6 mutation complicated by protein losing enteropathy has been reported. GATA6 gene is known to be involved in intestinal development with hepatobiliary malformations and gut abnormalities. [38]

Hennekam syndrome is associated with widespread congenital lymphatic dysplasia that presents with lymphedema, lymphangiectasia, and intellectual disability. One cause of this syndrome is mutation in CCBE1 (collagen and calcium-binding epidermal-growth factor domain containing protein-1). One report describes affected siblings with a marked decrease of this protein in lymphatics but not in mucosal blood vessels or muscularis mucosae. [39] Another report described a 5-week-old Pakistani girl with consanguineous parents who had PLE that resolved; however, lymphedema persisted in her extremities, with normal development. [40]  Another report of Hennekam syndrome resulted in thyroid and intestinal lymphangiectasia, leading to hypothyroidism and PLE. The hypothyroidism in this case required very high levothyroxine dosage due to its malabsorption in the gut. [41]

PLE was documented in a 4-month-old breastfed girl who presented with failure to thrive, erythema, and edema. She was found to have egg allergy; maternal dietary adjustment along with cromolyn and epinastine resolved the symptoms. [42]

Differential Diagnoses