Endocrine Abstracts

Introduction: HNF-1β maturity-onset diabetes of the young (MODY5) is uncommon, nevertheless accurate diagnosis guides individualized management and informs prognosis in probands and relatives.

Objective: To emphasize the importance of the appropriate use of clinical, biochemical and genetic investigations for the correct classification of diabetes etiology.

Case-report: A 35-year-old overweight Latin-American male was diagnosed with ketosis-prone A-β+ diabetes mellitus, however, due to a strong family history of diabetes with an autosomal dominant inheritance pattern, a niece with polycystic kidney disease during childhood, negativity for pancreatic β-Cell antibodies, and a C-peptide of 237 ng/ml, HNF-1β- MODY was suspected, further investigation revealed aplasia of the dorsal pancreas. The diagnosis was confirmed by the identification of a missense mutation (M_000458.2:c.884G>A (p.R295H) in the DNA-binding homeodomain of the HNF-1b gene (1).

Methods: Systematic clinical, biochemical characterization and HNF-1β mutational analysis were implemented to determine the diabetes etiology in four relatives.

Results: Identification of the p.R295H mutation in the proband’s maternal half brother and sister confirmed the diagnosis of HNF-1β-MODY, they were previously misclassified as having type 1 and type 2 diabetes respectively. A mutation analysis of his two sons, who did not meet diabetes criteria at the time of evaluation, revealed the p.R295H mutation, a diminished glomerular filtration rate with renal cysts, and aplasia of the dorsal pancreas only in the elder son. The proband’s other sister and adolescent niece had a diagnosis of diabetes mellitus and polycystic kidney disease but they were not able for testing nor his mother with diabetes but already deceased.

Conclusions: Two previously misclassified family members were shown to have HNF-1β- MODY, whereas another was shown to have clinical features associated with the mutation (pancreatic atrophy and chronic kidney failure with renal cysts) but no diabetes yet. This family exemplifies the importance of careful phenotyping and systematic evaluation of relatives after discovering monogenic diabetes in an individual since it has unique management, prognostic and genetic counseling implications.

Reference

Silva, C., Fernandez, E., Romero, J. and Martinez, G. (2017). Maturity-onset diabetes of the young type 5 (mody 5): a case report. Endocrine Abstracts.