Medical College of Wisconsin
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Case report: Two unexpected cases of DGUOK-related mitochondrial DNA depletion syndrome presenting with hyperinsulinemic hypoglycemia. Front Endocrinol (Lausanne) 2023;14:1268135

Date

11/29/2023

Pubmed ID

38027095

Pubmed Central ID

PMC10646319

DOI

10.3389/fendo.2023.1268135

Scopus ID

2-s2.0-85176586556 (requires institutional sign-in at Scopus site)

Abstract

Timely diagnosis of persistent neonatal hypoglycemia is critical to prevent neurological sequelae, but diagnosis is complicated by the heterogenicity of the causes. We discuss two cases at separate institutions in which clinical management was fundamentally altered by the results of molecular genetic testing. In both patients, critical samples demonstrated hypoketotic hypoglycemia and a partial glycemic response to glucagon stimulation, thereby suggesting hyperinsulinism (HI). However, due to rapid genetic testing, both patients were found to have deoxyguanosine kinase (DGUOK)-related mitochondrial DNA depletion syndrome, an unexpected diagnosis. Patients with this disease typically present with either hepatocerebral disease in the neonatal period or isolated hepatic failure in infancy. The characteristic features involved in the hepatocerebral form of the disease include lactic acidosis, hypoglycemia, cholestasis, progressive liver failure, and increasing neurologic dysfunction. Those with isolated liver involvement experience hepatomegaly, cholestasis, and liver failure. Although liver transplantation is considered, research has demonstrated that for patients with DGUOK-related mitochondrial DNA depletion syndrome and neurologic symptoms, early demise occurs. Our report advocates for the prompt initiation of genetic testing in patients presenting with persistent neonatal hypoglycemia and for the incorporation of mitochondrial DNA depletion syndromes in the differential diagnosis of HI.

Author List

Guzman H, Yazdani S, Harmon JL, Chapman KA, Vitola B, Pyle L, McKnight H, Sigal W, Lord K, De Leon DD, Merchant N, Ganetzky R

Author

Bernadette Vitola MPH, MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cholestasis
DNA, Mitochondrial
Humans
Hyperinsulinism
Hypoglycemia
Infant, Newborn
Liver Failure
Mitochondrial Diseases
Mutation
Phosphotransferases (Alcohol Group Acceptor)