A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia

ABSTRACT: Objective: To report a case of diabetes mellitus (DM) associated with partial pancreatic agenesis and congenital heart disease (CHD) in a patient found to have a nonsense mutation of the GATA6 gene. Methods: We present the imaging, laboratory, and genetic findings, and describe the clinic...

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Main Authors: Michelle L. Miles, DO, MS, Natasha Cowan, BS, Gavin Jackson, MD, FACE
Format: Article
Language:English
Published: Elsevier 2020-05-01
Series:AACE Clinical Case Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2376060520300146
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spelling doaj-6421d427ad214e32816d580f0939f50c2021-04-30T07:23:12ZengElsevierAACE Clinical Case Reports2376-06052020-05-0163e123e126A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic HypoplasiaMichelle L. Miles, DO, MS0Natasha Cowan, BS1Gavin Jackson, MD, FACE2From the Department of Internal Medicine, Scripps Mercy Hospital; Address correspondence to Dr. Michelle Miles, Department of Internal Medicine, 4077 Fifth Avenue, San Diego, CA 92103.School of Medicine, University of California San Diego, San Diego, California.From the Department of Internal Medicine, Scripps Mercy HospitalABSTRACT: Objective: To report a case of diabetes mellitus (DM) associated with partial pancreatic agenesis and congenital heart disease (CHD) in a patient found to have a nonsense mutation of the GATA6 gene. Methods: We present the imaging, laboratory, and genetic findings, and describe the clinical course of a patient with an atypical presentation of DM as well as CHD, who was found to have partial pancreatic agenesis on computed tomography (CT) imaging. Genetic testing was performed to identify monogenic DM. Results: A 30-year-old nonobese female with a waxing and waning pattern of insulin-dependent DM diagnosed at the age of 20 was found to have partial pancreatic agenesis on CT scan. It was unclear whether the patient was experiencing undetected hyperglycemia prior to initial diagnosis of DM. She had no history of diabetic ketoacidosis (DKA) despite poorly-controlled diabetes and years without insulin treatment. The patient also had congenital tricuspid atresia, ventricular septal defect, and transposition of the great vessels with surgical correction in childhood. Partial pancreatic agenesis and CHD with atypical DM prompted genetic testing for monogenic DM, and a nonsense mutation of the GATA6 (c.1242C>A, p.C414*) gene was found. Conclusion: GATA6 mutations are associated with a broad spectrum of diabetic phenotypes, pancreatic agenesis, and a variety of CHDs. This case highlights the importance of considering monogenic diabetes in young, nonobese patients with diabetes, particularly with negative pancreatic antibodies and no history of DKA. Further, this case demonstrates the importance of testing for GATA6 mutations in any young patient with diabetes and CHD.http://www.sciencedirect.com/science/article/pii/S2376060520300146
collection DOAJ
language English
format Article
sources DOAJ
author Michelle L. Miles, DO, MS
Natasha Cowan, BS
Gavin Jackson, MD, FACE
spellingShingle Michelle L. Miles, DO, MS
Natasha Cowan, BS
Gavin Jackson, MD, FACE
A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia
AACE Clinical Case Reports
author_facet Michelle L. Miles, DO, MS
Natasha Cowan, BS
Gavin Jackson, MD, FACE
author_sort Michelle L. Miles, DO, MS
title A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia
title_short A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia
title_full A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia
title_fullStr A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia
title_full_unstemmed A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia
title_sort nonsense gata6 mutation explains history of congenital heart defects and 10 years of poorly-controlled diabetes lacking dka in a non-obese 30 year-old incidentally found to have pancreatic hypoplasia
publisher Elsevier
series AACE Clinical Case Reports
issn 2376-0605
publishDate 2020-05-01
description ABSTRACT: Objective: To report a case of diabetes mellitus (DM) associated with partial pancreatic agenesis and congenital heart disease (CHD) in a patient found to have a nonsense mutation of the GATA6 gene. Methods: We present the imaging, laboratory, and genetic findings, and describe the clinical course of a patient with an atypical presentation of DM as well as CHD, who was found to have partial pancreatic agenesis on computed tomography (CT) imaging. Genetic testing was performed to identify monogenic DM. Results: A 30-year-old nonobese female with a waxing and waning pattern of insulin-dependent DM diagnosed at the age of 20 was found to have partial pancreatic agenesis on CT scan. It was unclear whether the patient was experiencing undetected hyperglycemia prior to initial diagnosis of DM. She had no history of diabetic ketoacidosis (DKA) despite poorly-controlled diabetes and years without insulin treatment. The patient also had congenital tricuspid atresia, ventricular septal defect, and transposition of the great vessels with surgical correction in childhood. Partial pancreatic agenesis and CHD with atypical DM prompted genetic testing for monogenic DM, and a nonsense mutation of the GATA6 (c.1242C>A, p.C414*) gene was found. Conclusion: GATA6 mutations are associated with a broad spectrum of diabetic phenotypes, pancreatic agenesis, and a variety of CHDs. This case highlights the importance of considering monogenic diabetes in young, nonobese patients with diabetes, particularly with negative pancreatic antibodies and no history of DKA. Further, this case demonstrates the importance of testing for GATA6 mutations in any young patient with diabetes and CHD.
url http://www.sciencedirect.com/science/article/pii/S2376060520300146
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