Maturity‐onset diabetes of the young: Different diabetes in an infant with cystic fibrosis

Abstract

Cystic fibrosis (CF) is one of the most common autosomal recessive and multisystemic diseases. CF affects many systems. One of these systems is the endocrine and exocrine functions of the pancreas, causing cystic fibrosis‐related diabetes, which is extremely complex and has unique pathogenesis. Maturity‐onset diabetes of the young (MODY) is a rare type of diabetes with autosomal dominant inheritance and is not expected in patients with CF. In this study, we present MODY due to a novel glucokinase gene mutation, which is an unexpected form of diabetes in patients with CF. This is previously unreported in the literature.

Clinical and Genetic Features of Maturity-onset Diabetes of the Young in Pediatric Patients: a 12-year Monocentric Experience

“…The coexistence of GCK MODY and cystic brosis is very rare. To the best of our knowledge, only two other cases of children suffering from both cystic brosis and GCK-MODY have been reported in literature [40,41]. It is well known that patients with cystic brosis have a gradual deterioration in their glucose tolerance status that begins in the rst years of the disease leading to the onset of cystic brosis related diabetes (CFRD) [42].…”

Monogenic Diabetes in a Child with Cystic Fibrosis: A Case Report and Review of the Literature

“…There are more than 600 reported mutations in GCK [ 12 ]. Autosomal dominant heterozygous inactivating mutations in GCK result in decreased sensitivity of pancreatic β-cells and a raised threshold for glucose-stimulated insulin secretion [ 8 , 9 ]. Patients with GCK-MODY typically present with mild, nonprogressive fasting hyperglycemia with HbA1c values ranging from 6% to 7.3% and relatively small increases in 2-hour OGTT glucose values [ 7-9 ].…”

“…Patients with GCK-MODY typically present with mild, nonprogressive fasting hyperglycemia with HbA1c values ranging from 6% to 7.3% and relatively small increases in 2-hour OGTT glucose values [ 7-9 ]. Patients with GCK-MODY do not develop the microvascular or macrovascular complications typically associated with other forms of diabetes and therefore do not require regular glucose monitoring or pharmacologic treatment with insulin or oral hypoglycemic agents, apart from during pregnancy [ 7 , 9 ]. In fact, patients with GCK-MODY treated with oral medications or insulin have higher rates of adverse events, particularly hypoglycemia [ 9 ].…”

“…All 3 siblings ultimately started sulfonylurea therapy, the targeted treatment for HNF1A mutations, which led to significant improvement in glycemic control. Hangul et al described an infant with CF (homozygous delF508) incidentally discovered to have persistent mild hyperglycemia since day-of-life 30 [ 9 ]. Low-dose insulin was started; however, subsequent genetic testing revealed a de novo heterozygous mutation in the GCK gene at c.1086_1090delCGACT p.D363RfsX94).…”

“…The presence of a GCK mutation in a patient with CF raises several important clinical concerns. Although the mild hyperglycemia caused by GCK-MODY typically does not require pharmacologic therapy, mild glycemic abnormalities in patients with CF have been associated with pulmonary decline and nutritional compromise [ 3 , 7 , 9 , 14 ]. When plasma glucose levels exceed 140 mg/dL, glucose becomes detectable in airway surface liquid, providing an enriched medium for the proliferation of CF pathogens and impacting neutrophil chemotaxis and function [ 4 , 14 ].…”