Somatic PTPN11 Mutation in a Child With Neuroblastoma and Protein Losing Enteropathy.

Neuroblastoma and protein losing enteropathy (PLE) are diagnoses commonly seen by oncologists and gastroenterologists, respectively. The concurrence of these 2 entities is rare, and not well explained. We describe the sixth case of PLE in a child with neuroblastoma, and the first for which genetic information is available. Tumor DNA had a mutation in the PTPN11 gene, which has been described in neuroblastoma, and in Noonan syndrome-a diagnosis in which neuroblastoma and PLE independently have been reported. Constitutional DNA was normal. Genetic studies in future patients will be needed to support the link between neuroblastoma and PLE.

Protein-losing enteropathy in dogs is associated with decreased fecal proteolytic activity.

BACKGROUND: Measurement of proteolytic activity in feces is a traditional method for the diagnosis of exocrine pancreatic insufficiency (EPI). A drawback of this method is the occurrence of falsely low results that may lead to a false-positive diagnosis of EPI. We hypothesized that intestinal loss of serum proteinase inhibitors in protein-losing enteropathy (PLE) may inhibit fecal proteolytic activity and be a potential source of false low results. OBJECTIVE: The objective of this study was to determine the effect of PLE on fecal proteolytic activity in dogs. METHODS: Fecal proteolytic activity was measured using a radial diffusion casein digestion assay in 12 samples from 4 clinically healthy control dogs and 30 samples from 16 dogs with PLE. Gastrointestinal protein loss was assessed using an ELISA to determine fecal canine alpha 1-proteinase inhibitor concentration. The relationship between the concentration of canine alpha 1-proteinase inhibitor in the feces and the diameter cleared in the casein digestion assay was determined. The mean clearing diameter was compared between control dogs and dogs with PLE. RESULTS: A significant negative correlation was observed between fecal canine alpha1-proteinase inhibitor concentration and casein clearing diameter (P <.001, Pearson r =.6317, r2 =.3999). Mean clearing diameter was significantly lower in dogs with PLE than in control dogs (12.63 vs 16.83 mm, P <.001, two-tailed Student's t-test). CONCLUSION: Increased fecal loss of alpha1-proteinase inhibitor in dogs with PLE is associated with a significant decrease in fecal proteolytic activity and may result in a false positive diagnosis of EPI.

Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy.

Phosphomannose isomerase (PMI) deficiency is the cause of a new type of carbohydrate-deficient glycoprotein syndrome (CDGS). The disorder is caused by mutations in the PMI1 gene. The clinical phenotype is characterized by protein-losing enteropathy, while neurological manifestations prevailing in other types of CDGS are absent. Using standard diagnostic procedures, the disorder is indistinguishable from CDGS type Ia (phosphomannomutase deficiency). Daily oral mannose administration is a successful therapy for this new type of CDG syndrome classified as CDGS type Ib.

[Alpha 1-antitrypsin as an endogenous marker of protein-losing enteropathies]. / Alpha 1-antytrypsyna endogennym markerem jelitowej ucieczki bialka.

A novelty of the present studies is the use of alpha 1-antitrypsin (A-1--AT) as an endogenous marker of enteric protein loss. Enteric clearance of alpha 1-antitrypsin was determined in 10 patients with the symptoms of PLE, and in 6 healthy individuals. Alpha 1-Antitrypsin concentration has been assayed in single, random samples of feces collected from 42 patients and 12 healthy individuals (normal values: 1.31 +/- 0.72 mg/g of feces). Markedly increased enteric clearance and A-1-AT concentrations in single, random samples of feces have been found in patients with enteric lymphangiectasis, Crohn's disease, ulcerative colitis, and constrictive pericarditis, slightly lower in coeliac, chronic diarrhoea, nonspecific hemorrhagic colitis, esophagitis, lambliasis, hypogammaglobulinemia, Wiskott-Aldrich syndrome, Rendu-Osler-Weber syndrome, hepatitis in newborn, and Gilbert's disease. Statistically significant positive clearance has been noted (r = 0.997; p less than .001). A single assay of A-1-AT in feces is simple, repeatable, and sensitive technique in the diagnosis and evaluation of these diseases in which the symptoms of enteric protein loss are seen.

Fecal intestinal alkaline phosphatase in coeliac disease.

The intestinal alkaline phosphatase (I-AP) in feces was investigated in 16 patients with adult coeliac disease and 2 patients with gluten-sensitive enteropathy in dermatitis herpetiformis using an immunoprecipitation method. The mean concentration of I-AP activity in feces was reduced by 76% in patients with coeliac disease in comparison to normal controls (11.5 : 47.5 U/g). Patients with total villous atrophy (mean = 5.3 U/g) demonstrated a lower activity than patients with partial villous atrophy (mean = 14.3 U/g). Follow-up studies showed stable fecal I-AP-activities in symptom-free patients, whereas patients with relapses were characterized by fluctuating activities. The administration of a single oral dose of 31 g gluten is followed by a fecal I-AP-excretion pattern similar to toxic damage of the small bowel mucosa.