Abstract
BackgroundHeterozygous mutations in the HNF1B gene are the most common monogenic cause of developmental kidney disease. Extrarenal phenotypes frequently occur, including diabetes mellitus and pancreatic hypoplasia; the latter is associated with subclinical exocrine dysfunction. We measured faecal elastase-1 in patients with HNF1B-associated disease regardless of diabetes status and assessed the degree of symptoms associated with pancreatic exocrine deficiency.MethodsFaecal elastase-1 was measured in 29 patients with a known HNF1B mutation. We defined a low faecal elastase-1 concentration based on the 2.5 percentile of 99 healthy control individuals (410 μg/g stool). Symptoms related to pancreatic exocrine dysfunction were assessed and a subset of the HNF1B cohort (n = 6) underwent pancreatic imaging.ResultsFaecal elastase-1 was below the 2.5 percentile of the control cohort in 18/29 (62%) patients with HNF1B-associated renal disease. A total of 8/29 (28%) had a measurement suggestive of exocrine pancreatic insufficiency at <200 μg/g stool; of these, 3 suffered with abdominal pain, loose stools and/or unintentional weight loss. All three experienced symptomatic improvement and weight gain after commencing pancreatic enzyme replacement therapy. Faecal elastase-1 was low in 7/15 (47%) HNF1B patients without diabetes compared with 11/14 (79%) of those with diabetes (P = 0.1).ConclusionsFaecal elastase-1 deficiency is a common feature of HNF1B-associated renal disease even when diabetes is not present and pancreatic exocrine deficiency may be more symptomatic than previously suggested. Faecal elastase-1 should be measured in all patients with known HNF1B-associated disease complaining of chronic abdominal pain, loose stools or unintentional weight loss. The discovery of a low faecal elastase-1 concentration in individuals with developmental kidney disease of uncertain cause should prompt referral for HNF1B genetic testing.
Highlights
Hepatocyte nuclear factor 1b (HNF1B) is a transcription factor with important roles in the development of the kidney, pancreas, liver and genital tract [1]
A total of 3/8 individuals with a faecal elastase-1 measurement
We have demonstrated that faecal elastase-1 deficiency is common in HNF1B-associated renal disease and exocrine pancreatic dysfunction may be more symptomatic than previously published
Summary
Hepatocyte nuclear factor 1b (HNF1B) is a transcription factor with important roles in the development of the kidney, pancreas, liver and genital tract [1]. Heterozygous mutations of the HNF1B gene are the most common known monogenic cause of developmental kidney disease [2,3,4] Despite this single genetic aetiology, the phenotype of HNF1B-associated renal disease is very variable (Box 1). Genetic changes comprise either HNF1B intragenic mutations (one-half of patients) or an approximate 1.3-Mb deletion at chromosome 17q12, which includes the entire HNF1B gene [13, 14] Both may arise spontaneously, which means there is often no family history of renal disease or diabetes [15,16,17]. Faecal elastase-1 should be measured in all patients with known HNF1B-associated disease complaining of chronic abdominal pain, loose stools or unintentional weight loss. The discovery of a low faecal elastase-1 concentration in individuals with developmental kidney disease of uncertain cause should prompt referral for HNF1B genetic testing
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