From diarrhea to obesity in prohormone convertase 1/3 deficiency: age-dependent clinical, pathologic, and enteroendocrine characteristics

Bandsma, Robert H. J.; Sokollik, Christiane; Chami, Rose; Cutz, Ernest; Brubaker, Patricia L.; Hamilton, Jill K.; Perlman, Kusiel; Zlotkin, Stanley; Sigalet, David L.; Sherman, Philip M.; Martin, Martin G.; Avitzur, Yaron (2013). From diarrhea to obesity in prohormone convertase 1/3 deficiency: age-dependent clinical, pathologic, and enteroendocrine characteristics. Journal of clinical gastroenterology, 47(10), pp. 834-843. Lippincott Williams & Wilkins 10.1097/MCG.0b013e3182a89fc8

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GOALS The aim of this report is to delineate the clinical, pathologic, and enteroendocrine (EE) features of prohormone convertase 1/3 (PC1/3) deficiency in children. BACKGROUND Prohormone convertases play a pivotal role in the activation of biologically inactive hormones. Congenital defects in the EE axis, such as PC1/3 deficiency, have been rarely reported and their pathophysiological mechanisms are largely unknown. STUDY EE function and pathology was evaluated in 4 males (1, 2, 7, and 10 y old) from 2 families with PC1/3 deficiency at a university children's hospital. Clinical course, pathology analysis including immunohistochemistry for PC1/3, PC2, and glucagon-like peptide 1 (GLP-1) and electron microscopy, as well as EE function tests (GLP-1, GLP-2, oral glucose tolerance test) were performed. RESULTS All (n=4) suffered from congenital severe diarrhea associated with malabsorption. The diarrhea improved during the first year of life and hyperphagia with excessive weight gain (BMI>97th percentile) became the predominant phenotype at an older age. Analysis of the enteroendocrine axis revealed high proinsulin levels (57 to 1116 pmol/L) in all patients, low serum GLP-2 levels, and impaired insulin and GLP-1 secretion after an oral glucose tolerance test at a young age, with improvement in 1 older child tested. Electron microscopy showed normal ultrastructure of enterocytes and EE cells. Immunohistochemistry revealed normal expression of chromogranin A, a marker of EE cells but markedly reduced immunostaining for PC1/3 and PC2 in all patients. CONCLUSIONS PC1/3 deficiency is associated with an age dependent, variable clinical phenotype caused by severe abnormalities in intestinal and EE functions. Serum level of proinsulin can be used as an effective screening tool.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Gastroenterology

UniBE Contributor:

Sokollik, Christiane

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0192-0790

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Christiane Sokollik

Date Deposited:

11 Jun 2014 17:12

Last Modified:

11 Jun 2014 17:12

Publisher DOI:

10.1097/MCG.0b013e3182a89fc8

PubMed ID:

24135795

URI:

https://boris.unibe.ch/id/eprint/45599

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