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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort
Gastroenterology, Volume 145, No. 1, Year 2013
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Description
Background & Aims: Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 also have been associated with obesity in heterozygotes in several population-based studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency. Methods: We studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins. Results: We identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears. Conclusions: In a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in the processing of one or more enteric hormones that are required for nutrient absorption. © 2013 by the AGA Institute.
Authors & Co-Authors
Martín, Martín G.
United States, Los Angeles
Ucla Mattel Children's Hospital
Lindberg, Iris
United States, Baltimore
University of Maryland, Baltimore Umb
Solorzano-Vargas, R. Sergio
United States, Los Angeles
Ucla Mattel Children's Hospital
Wang, Jiafang
United States, Los Angeles
Ucla Mattel Children's Hospital
Avitzur, Yaron
Canada, Toronto
Hospital for Sick Children University of Toronto
Bandsma, Robert H.J.
Canada, Toronto
Hospital for Sick Children University of Toronto
Sokollik, Christiane
Canada, Toronto
Hospital for Sick Children University of Toronto
Lawrence, Sarah
Canada, Ottawa
Children's Hospital of Eastern Ontario, Ottawa
Pickett, Lindsay A.
United States, Baltimore
University of Maryland, Baltimore Umb
Chen, Zijun
United States, Los Angeles
Ucla Mattel Children's Hospital
Egritas, Odul
Turkey, Ankara
Gazi University, Faculty of Medicine
Dalgic, Buket
Turkey, Ankara
Gazi University, Faculty of Medicine
Albornoz, Valeria
United States, Baltimore
University of Maryland, Baltimore Umb
De Ridder, Lissy
Netherlands, Rotterdam
Erasmus Mc Sophia Children’s Hospital
Hulst, Jessie
Netherlands, Rotterdam
Erasmus Mc Sophia Children’s Hospital
Gok, Faysal
Turkey, Ankara
Gülhane Eğitim ve Araştırma Hastanesi
Aydoǧan, Ayşen
Turkey, Izmir
Kocaeli Üniversitesi
Al-Hussaini, Abdulrahman Abdullah
Saudi Arabia, Riyadh
King Fahad Medical City
Gok, Deniz Engin
Turkey, Ankara
Gülhane Eğitim ve Araştırma Hastanesi
Yourshaw, Michael
United States, Los Angeles
David Geffen School of Medicine at Ucla
Wu, S. Vincent
United States, Los Angeles
Va Greater Los Angeles Healthcare System
Cortina, Galen
United States, Los Angeles
David Geffen School of Medicine at Ucla
Stanford, Sara
United States, Los Angeles
Ucla Mattel Children's Hospital
Georgia, Senta
United States, Los Angeles
David Geffen School of Medicine at Ucla
Statistics
Citations: 133
Authors: 24
Affiliations: 11
Identifiers
Doi:
10.1053/j.gastro.2013.03.048
ISSN:
00165085
e-ISSN:
15280012
Research Areas
Food Security
Genetics And Genomics
Maternal And Child Health
Noncommunicable Diseases
Study Design
Cross Sectional Study
Cohort Study
Participants Gender
Male