Reclassification of diabetes etiology in a family with multiple diabetes phenotypes.
J Clin Endocrinol Metab
; 99(6): E1067-71, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24606082
ABSTRACT
BACKGROUND:
Maturity-onset diabetes of the young (MODY) is uncommon; however, accurate diagnosis facilitates personalized management and informs prognosis in probands and relatives.OBJECTIVE:
The objective of the study was to highlight that the appropriate use of genetic and nongenetic investigations leads to the correct classification of diabetes etiology. CASEDISCUSSION:
A 30-year-old European female was diagnosed with insulin-treated gestational diabetes. She discontinued insulin after delivery; however, her fasting hyperglycemia persisted. ß-Cell antibodies were negative and C-peptide was 0.79 nmol/L. Glucokinase (GCK)-MODY was suspected and confirmed by the identification of a GCK mutation (p.T206M).METHODS:
Systematic clinical and biochemical characterization and GCK mutational analysis were implemented to determine the diabetes etiology in five relatives. Functional characterization of GCK mutations was performed.RESULTS:
Identification of the p.T206M mutation in the proband's sister confirmed a diagnosis of GCK-MODY. Her daughter was diagnosed at 16 weeks with permanent neonatal diabetes (PNDM). Mutation analysis identified two GCK mutations that were inherited in trans-p. [(R43P);(T206M)], confirming a diagnosis of GCK-PNDM. Both mutations were shown to be kinetically inactivating. The proband's mother, other sister, and daughter all had a clinical diagnosis of type 1 diabetes, confirmed by undetectable C-peptide levels and ß-cell antibody positivity. GCK mutations were not detected.CONCLUSIONS:
Two previously misclassified family members were shown to have GCK-MODY, whereas another was shown to have GCK-PNDM. A diagnosis of type 1 diabetes was confirmed in three relatives. This family exemplifies the importance of careful phenotyping and systematic evaluation of relatives after discovering monogenic diabetes in an individual.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transtornos Puerperais
/
Diabetes Gestacional
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Adult
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Female
/
Humans
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Pregnancy
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article