Exocrine pancreatic function in hepatocyte nuclear factor 1β‐maturity‐onset diabetes of the young (<scp>HNF</scp>1B‐<scp>MODY</scp>) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas

Tjora, Erling; Wathle, Gaute Kjellevold; Erchinger, Friedemann; Engjom, Trond; Molven, Anders; Aksnes, Lage; Haldorsen, Ingfrid S.; Ræder, Helge; Njølstad, Pål R.

doi:10.1111/dme.12190

Cited by 29 publications

(30 citation statements)

References 27 publications

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“…In addition to insulin deficiency related to pancreatic hypoplasia, patients also show some degree of hepatic insulin resistance, which explains why they do not respond adequately to sulfonylurea treatment and require early insulin therapy . Moreover, mutation carriers have lower exocrine pancreatic function with reduced fecal elastase; this involves both ductal and acinar cells . Therefore, the phenotype of RCAD patients is highly variable even within families sharing the same HNF1B mutation and therefore this diagnosis should be considered not only in the diabetes clinic but also in other clinics (nephrology, urology, gynecology, etc.).…”

Section: Genetic Syndromes Associated With Diabetesmentioning

confidence: 99%

ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents

et al. 2018

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Section: Genetic Syndromes Associated With Diabetesmentioning

confidence: 99%

ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents

et al. 2018

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“…9,10 Detailed assessments of pancreatic function, using rapid endoscopic secretin stimulation tests and secretin-stimulated MRI, have confirmed this co-morbidity among patients with HNF1B-associated disease. 79 Pancreatic exocrine hypersecretion has also been observed in affected individuals, and could be a compensatory mechanism for diminished pancreatic volume. These data suggest that the small pancreas observed in individuals with HNF1B mutations might be the result of hypoplasia rather than atrophy.…”

Section: Extra-renal Phenotypesmentioning

confidence: 99%

HNF1B-associated renal and extra-renal disease—an expanding clinical spectrum

Hamilton²,

et al. 2014

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Heterozygous mutations in the gene that encodes the transcription factor hepatocyte nuclear factor 1β (HNF1B) represent the most common known monogenic cause of developmental kidney disease. Renal cysts are the most frequently detected feature of HNF1B-associated kidney disease; however, other structural abnormalities, including single kidneys and renal hypoplasia, and electrolyte abnormalities can also occur. Extra-renal phenotypes might also be observed; consequently, HNF1B-associated disease is considered a multi-system disorder. Other clinical features include early-onset diabetes mellitus, pancreatic hypoplasia, genital tract malformations, abnormal liver function and early-onset gout. Heterozygous mutations in the coding region or splice sites of HNF1B, and complete gene deletion, each account for ∼50% of all cases of HNF1B-associated disease, respectively, and often arise spontaneously. There is no clear genotype-phenotype correlation, consistent with haploinsufficiency as the disease mechanism. Data from animal models suggest that HNF1B has an important function during several stages of nephrogenesis; however, the precise signalling pathways remain to be elucidated. This Review discusses the genetics and molecular pathways that lead to disease development, summarizes the reported renal and extra-renal phenotypes, and identifies areas for future research in HNF1B-associated disease.

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“…When checked carefully, subclinical dysfunction in the form of reduced bicarbonate and enzyme secretion can be found in mutation carriers compared with controls [46].…”

Section: Exocrine Pancreas Dysfunctionmentioning

confidence: 99%

HNF1B-associated clinical phenotypes: the kidney and beyond

2015

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Mutations in HNF1B, the gene encoding hepatocyte nuclear factor 1β are the most commonly identified genetic cause of renal malformations. HNF1B was first identified as a disease gene for diabetes (MODY5) in 1997, and its involvement in renal disease was subsequently noted through clinical observations in pedigrees affected by MODY5. Since then, a whole spectrum of associated phenotypes have been reported, including genital malformations, autism, epilepsy, gout, hypomagnesaemia, primary hyperparathyroidism, liver and intestinal abnormalities and a rare form of kidney cancer. The most commonly identified mutation, in approximately 50 % of patients, is an entire gene deletion occurring in the context of a 17q12 chromosomal microdeletion that also includes several other genes. Some of the associated phenotypes, especially the neurologic ones, appear to occur only in the context of this microdeletion and thus may not be directly linked to HNF1B. Here we review the spectrum of associated phenotypes and discuss potential implications for clinical management.

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Exocrine pancreatic function in hepatocyte nuclear factor 1β‐maturity‐onset diabetes of the young (HNF1B‐MODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas

Abstract: Carriers of the HNF1B mutation have lower exocrine pancreatic function involving both ductal and acinar cells. Compensatory hypersecretion suggests that the small pancreas of HNF1B mutation carriers is attributable to hypoplasia, not atrophy.

Cited by 29 publications

References 27 publications

ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents

ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents

HNF1B-associated renal and extra-renal disease—an expanding clinical spectrum

HNF1B-associated clinical phenotypes: the kidney and beyond

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