Enteroendocrine Dysfunction in Two Saudi Sisters

Overview

Journal Case Rep Gastroenterol

Publisher Karger

Specialty Gastroenterology

Date 2021 Apr 1

PMID 33790717

Citations 4

Authors

Amna Basheer M Ahmed

Badr M Rasheed Alsaleem

Affiliations

Soon will be listed here.

Abstract

Proprotein convertase (PC) deficiency is a rare autosomal recessive disorder caused by mutations in proprotein convertase subtilisin/kexin type 1 (). It is characterized by severe malabsorptive early-onset diarrhea, obesity, and systemic endocrinopathies. Only few cases have been reported in the literature; we have add two female sisters with some difference in clinical progress. Herein, we describe two sisters with congenital osmotic diarrhea diagnosed with PC1/3 deficiency, causing malabsorptive diarrhea and enteroendocrine dysfunction, who presented with chronic enteropathy with hypernatremia but with different expressivity. PC1/3 deficiency presents with symptoms and signs that mimic glucose-galactose malabsorption. Because of the clinical paucity and heterogeneity of congenital enteropathies, whole-exome sequencing may be of great help towards early diagnosis and effective treatment.

Citing Articles

Enteroendocrine cell regulation of the gut-brain axis.

Barton J, Londregan A, Alexander T, Entezari A, Covarrubias M, Waldman S Front Neurosci. 2023; 17:1272955.

PMID: 38027512 PMC: 10662325. DOI: 10.3389/fnins.2023.1272955.

Heterogeneity in biomarkers, mitogenome and genetic disorders of the Arab population with special emphasis on large-scale whole-exome sequencing.

Borgio J Arch Med Sci. 2023; 19(3):765-783.

PMID: 37313193 PMC: 10259412. DOI: 10.5114/aoms/145370.

Modulation of PC1/3 activity by a rare double-site homozygous mutation.

Ni Y, Chen X, Sun Y, Pan J, Tang C, Yuan T Front Pediatr. 2022; 10:1026707.

PMID: 36389395 PMC: 9659753. DOI: 10.3389/fped.2022.1026707.

Rare Heterozygous Variants in Human Obesity: The Contribution of the p.Y181H Variant and a Literature Review.

Van Dijck E, Beckers S, Diels S, Huybrechts T, Verrijken A, Van Hoorenbeeck K Genes (Basel). 2022; 13(10).

PMID: 36292633 PMC: 9601648. DOI: 10.3390/genes13101746.

References

Benzinou M, Creemers J, Choquet H, Lobbens S, Dina C, Durand E . Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet. 2008; 40(8):943-5. DOI: 10.1038/ng.177. View

Singleton A . Exome sequencing: a transformative technology. Lancet Neurol. 2011; 10(10):942-6. PMC: 3302356. DOI: 10.1016/S1474-4422(11)70196-X. View

Bandsma R, Sokollik C, Chami R, Cutz E, Brubaker P, Hamilton J . From diarrhea to obesity in prohormone convertase 1/3 deficiency: age-dependent clinical, pathologic, and enteroendocrine characteristics. J Clin Gastroenterol. 2013; 47(10):834-43. PMC: 3842618. DOI: 10.1097/MCG.0b013e3182a89fc8. View

Martin M, Turk E, Lostao M, Kerner C, Wright E . Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. Nat Genet. 1996; 12(2):216-20. DOI: 10.1038/ng0296-216. View

Muller T, Hess M, Schiefermeier N, Pfaller K, Ebner H, Heinz-Erian P . MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity. Nat Genet. 2008; 40(10):1163-5. DOI: 10.1038/ng.225. View

Jackson R, Creemers J, Farooqi I, Raffin-Sanson M, Varro A, Dockray G . Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest. 2003; 112(10):1550-60. PMC: 259128. DOI: 10.1172/JCI18784. View

Dong W, Seidel B, Marcinkiewicz M, Chretien M, Seidah N, Day R . Cellular localization of the prohormone convertases in the hypothalamic paraventricular and supraoptic nuclei: selective regulation of PC1 in corticotrophin-releasing hormone parvocellular neurons mediated by glucocorticoids. J Neurosci. 1997; 17(2):563-75. PMC: 6573246. View

Farooqi I, Volders K, Stanhope R, Heuschkel R, White A, Lank E . Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab. 2007; 92(9):3369-73. DOI: 10.1210/jc.2007-0687. View

Schaner P, Todd R, Seidah N, Nillni E . Processing of prothyrotropin-releasing hormone by the family of prohormone convertases. J Biol Chem. 1997; 272(32):19958-68. DOI: 10.1074/jbc.272.32.19958. View

10.

Harter B, Fuchs I, Muller T, Akbulut U, Cakir M, Janecke A . Early Clinical Diagnosis of PC1/3 Deficiency in a Patient With a Novel Homozygous PCSK1 Splice-Site Mutation. J Pediatr Gastroenterol Nutr. 2015; 62(4):577-80. DOI: 10.1097/MPG.0000000000001018. View

11.

Ramos-Molina B, Martin M, Lindberg I . PCSK1 Variants and Human Obesity. Prog Mol Biol Transl Sci. 2016; 140:47-74. PMC: 6082390. DOI: 10.1016/bs.pmbts.2015.12.001. View

12.

Philippe J, Stijnen P, Meyre D, De Graeve F, Thuillier D, Delplanque J . A nonsense loss-of-function mutation in PCSK1 contributes to dominantly inherited human obesity. Int J Obes (Lond). 2014; 39(2):295-302. DOI: 10.1038/ijo.2014.96. View

13.

Wilschanski M, Abbasi M, Blanco E, Lindberg I, Yourshaw M, Zangen D . A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1/3 and impairs its enzymatic activity. PLoS One. 2014; 9(10):e108878. PMC: 4182778. DOI: 10.1371/journal.pone.0108878. View

14.

Shendure J . Next-generation human genetics. Genome Biol. 2011; 12(9):408. PMC: 3308046. DOI: 10.1186/gb-2011-12-9-408. View

15.

Gonc E, Ozon A, Alikasifoglu A, Kandemir N . Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy. J Clin Res Pediatr Endocrinol. 2017; 9(3):283-287. PMC: 5596812. DOI: 10.4274/jcrpe.3986. View

16.

Yourshaw M, Solorzano-Vargas R, Pickett L, Lindberg I, Wang J, Cortina G . Exome sequencing finds a novel PCSK1 mutation in a child with generalized malabsorptive diarrhea and diabetes insipidus. J Pediatr Gastroenterol Nutr. 2013; 57(6):759-67. PMC: 4170062. DOI: 10.1097/MPG.0b013e3182a8ae6c. View

17.

Seidah N . The proprotein convertases, 20 years later. Methods Mol Biol. 2011; 768:23-57. DOI: 10.1007/978-1-61779-204-5_3. View

18.

Sivagnanam M, Mueller J, Lee H, Chen Z, Nelson S, Turner D . Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology. 2008; 135(2):429-37. PMC: 2574708. DOI: 10.1053/j.gastro.2008.05.036. View

19.

Creemers J, Choquet H, Stijnen P, Vatin V, Pigeyre M, Beckers S . Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity. Diabetes. 2012; 61(2):383-90. PMC: 3266396. DOI: 10.2337/db11-0305. View

20.

Martin M, Lindberg I, Solorzano-Vargas R, Wang J, Avitzur Y, Bandsma R . Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort. Gastroenterology. 2013; 145(1):138-148. PMC: 3719133. DOI: 10.1053/j.gastro.2013.03.048. View