trypsinogen and Celiac-Disease

Topics: Amino Acid Metabolism, Inborn Errors; Amino Acids; Biological Transport; Carboxypeptidases; Celiac Disease; Cell Membrane; Chymotrypsinogen; Diet; Dietary Proteins; Digestion; Enzyme Precursors; Gastric Mucosa; Hartnup Disease; Humans; Hydrolysis; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Pancreas; Pancreatic Elastase; Pepsin A; Peptide Hydrolases; Peptides; Trypsinogen

With the use of clinical data from a large international cohort, we evaluated and compared affected siblings and isolated cases.. Data from 116 families were collected, and patients conforming to our predetermined diagnostic criteria were analyzed. Phenotypic manifestations of affected siblings and singletons were compared with the use of t tests, Wilcoxon scores, and chi2 analysis.. Eighty-eight patients (33 female, 55 male; median age 5.20 years) fulfilled our predetermined diagnostic criteria for Shwachman syndrome; 63 patients were isolated cases, and 25 affected siblings were from 12 multiplex families. Steatorrhea was present in 86% (57 of 66), and 91% (78 of 86) displayed a low serum trypsinogen concentration. Patients older than 4 years more often had pancreatic sufficiency. Neutropenia occurred in 98%, anemia in 42%, and thrombocytopenia in 34%. Myelodysplasia or cytogenetic abnormalities were reported in 7 patients. Short stature with normal nutritional status was a prominent feature.. Clinical features among patients with Shwachman syndrome varied between patients and with age. Similarities in phenotype between isolated cases and affected sibling sets support the hypothesis that Shwachman syndrome is a single disease entity.

Topics: Bacterial Infections; Bone Diseases, Developmental; Celiac Disease; Child; Child, Preschool; Cohort Studies; Exocrine Pancreatic Insufficiency; Female; Growth Disorders; Hematologic Diseases; Hepatomegaly; Humans; Infant; Infant, Newborn; Male; Neutropenia; Nuclear Family; Phenotype; Statistics, Nonparametric; Syndrome; Trypsinogen

Topics: Biopsy; Celiac Disease; Coloring Agents; Feces; Humans; Intestine, Small; Malabsorption Syndromes; Pancreatic Function Tests; Radioimmunoassay; Trypsinogen; Xylose

A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac disease. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immuno-reactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.

Topics: Adolescent; Celiac Disease; Exocrine Pancreatic Insufficiency; Glutens; Growth Disorders; Humans; Male; Pancreatic Function Tests; Trypsinogen

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4.9 +/- 4.9 micrograms/l (mean +/- SD), significantly below values in patients with non-pancreatic steatorrhoea (47.0 +/- 22.1 micrograms/l, p less than 0.001) and 50 control subjects (31.4 +/- 7.4 micrograms/l, p less than 0.001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0.2-17.0 yr who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (less than -2SD or less than 16.6 micrograms/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (greater than or equal to 16.6 micrograms/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold.

Topics: Adolescent; Celiac Disease; Child; Child, Preschool; Humans; Infant; Pancreas; Pancreatic Diseases; Trypsin; Trypsinogen

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P less than .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Cations; Celiac Disease; Child; Child, Preschool; Cystic Fibrosis; Dietary Fats; Enzyme-Linked Immunosorbent Assay; Feces; Female; Gastrointestinal Contents; Humans; Lipase; Male; Pancreas; Radioimmunoassay; Trypsin; Trypsinogen

Topics: Celiac Disease; Humans; Pancreatic Diseases; Trypsinogen

Topics: Celiac Disease; Clinical Enzyme Tests; Exocrine Pancreatic Insufficiency; Humans; Pancreatitis; Radioimmunoassay; Reagent Kits, Diagnostic; Trypsin; Trypsinogen

Topics: Acute Disease; Adult; Animals; Cacodylic Acid; Callitrichinae; Cattle; Celiac Disease; Child; Chlorocebus aethiops; Chronic Disease; Dianisidine; Duodenum; Endopeptidases; Enteropeptidase; Guinea Pigs; Histocytochemistry; Humans; Intestine, Small; Mice; Mice, Inbred Strains; Oligopeptides; Pancreatitis; Rats; Swine; Swine, Miniature; Trypsinogen

Topics: Celiac Disease; Duodenum; Endopeptidases; Enteropeptidase; Glucagon; Humans; Intestinal Mucosa; Malabsorption Syndromes; Trypsin; Trypsinogen