RESUMEN
Congenital hyperinsulinemia (CHI) is a heterogeneous disorder characterized by persistent hypoglycemia due to inappropriate insulin secretion. A total of 15 gene mutations have already been reported to be associated with CHI. Among them, CHI caused by the GCK mutation is named GCK-CHI, which is considered to be a rare form of CHI. Here, we reported two cases of GCK-CHI diagnosed by genetic testing and summarized the clinical characteristics. In patients with recurrent or persistent hypoglycemia, CHI should be taken into consideration. Genetic testing should be perfomed in these patients to avoid misdiagnosis and provide accurate intervention, thus to improve prognosis.
Asunto(s)
Hiperinsulinismo Congénito , Humanos , Hiperinsulinismo Congénito/diagnóstico , Hiperinsulinismo Congénito/genética , Hiperinsulinismo Congénito/complicaciones , Mutación , Pruebas Genéticas , PronósticoRESUMEN
Introduction: The prevalence among pregnant women with diabetes of monogenic diabetes due to glucokinase deficit (GCK-MODY) varies from 0 to 80% in different studies, based on the chosen selection criteria for genetic test. New pregnancy-specific Screening Criteria (NSC), validated on an Anglo-Celtic pregnant cohort, have been proposed and include pre-pregnancy BMI <25 kg/m2 and fasting glycemia >99 mg/dl. Our aim was to estimate the prevalence of GCK-MODY and to evaluate the diagnostic performance of NSC in our population of women with diabetes in pregnancy. Patients and Methods: We retrospectively selected from our database of 468 diabetic pregnant patients in Sant'Andrea Hospital, in Rome, from 2010 to 2018, all the women who received a genetic test for GCK deficit because of specific clinical features. We estimated the prevalence of GCK-MODY among tested women and the minimum prevalence in our entire population with non-autoimmune diabetes. We evaluated diagnostic performance of NSC on the tested cohort and estimated the eligibility to genetic test based on NSC in the entire population. Results: A total of 409 patients had diabetes in pregnancy, excluding those with autoimmune diabetes; 21 patients have been tested for GCK-MODY, 8 have been positive and 13 have been negative (2 of them had HNF1-alfa mutations and 1 had HNF4-alfa mutation). We found no significant differences in clinical features between positive and negative groups except for fasting glycemia, which was higher in the positive group. The minimum prevalence of monogenic diabetes in our population was 2.4%. The minimum prevalence of GCK-MODY was 1.95%. In the tested cohort, the prevalence of GCK-MODY was 38%. In this group, NSC sensitivity is 87% and specificity is 30%, positive predictive value is 43%, and negative predictive value is 80%. Applying NSC on the entire population of women with non-autoimmune diabetes in pregnancy, 41 patients (10%) would be eligible for genetic test; considering a fasting glycemia >92 mg/dl, 85 patients (20.7%) would be eligible. Discussion: In our population, NSC have good sensitivity but low specificity, probably because there are many GDM with GCK-MODY like features. It is mandatory to define selective criteria with a good diagnostic performance on Italian population, to avoid unnecessary genetic tests.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Diabetes Gestacional/epidemiología , Glucoquinasa/deficiencia , Mutación , Embarazo en Diabéticas/epidemiología , Adulto , Biomarcadores/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/sangre , Diabetes Gestacional/enzimología , Diabetes Gestacional/genética , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Glucoquinasa/genética , Humanos , Italia/epidemiología , Embarazo , Embarazo en Diabéticas/sangre , Embarazo en Diabéticas/enzimología , Embarazo en Diabéticas/genética , Prevalencia , Pronóstico , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Fibrosis Quística/genética , Diabetes Mellitus Tipo 2/genética , Glucoquinasa/genética , Humanos , Lactante , Recién Nacido , Masculino , MutaciónRESUMEN
Maturity-onset diabetes of the young (MODY) is a clinically heterogenic group of diseases, with an autosomal dominant mode of inheritance and gene mutations resulting in dysfunction of pancreatic ß cells. The type of diabetes and further treatment policy can be reliably determined on the basis of the data of a molecular genetic study that confirms gene mutations. Today there are known mutations of 8 genes, of which glucokinase (GCK) gene mutation that leads to the development of MODY2 and occurs most frequently. The spread of this mutation among DM patients in our country has not been studied. The diagnosis of MODY2 was established in 13 members of 5 families with the clinical picture typical of this type. The molecular genetic study revealed 4 new and 1 earlier described mutations. The findings extend ideas on the molecular bases of MODY, which creates conditions for improving the diagnosis of this disease, genetic counseling and the development of pathogenetically founded approaches to treatment.