Challenges in diagnosis and treatment of KCNJ11-MODY

Autores da FMUP

• Jorge Manuel P. Pires Pedro

  Autor

• Paula Isabel Marques Simões De Freitas

  Autor

Participantes de fora da FMUP

• Goncalves, Juliana
• Ferreira, Helena Urbano
• Ribeiro, Sara
• da Rocha, Diogo Fernandes
• Souto, Selma B.
• Queiros, Joana

Unidades de investigação

• Medicina

Abstract

Maturity-onset diabetes of the young (MODY) is a subtype of monogenic diabetes and a rare type of diabetes, which accounts for 1-5% of cases and is often underdiagnosed. The importance of its diagnosis lies in the potential implications that it can have on disease management and offspring. We report a de novo KCNJ11-MODY case and the process of transition from insulin to sulfonylureas. A 24-year-old Caucasian woman was referred to the Endocrinology Department on account of newly diagnosed diabetes mellitus. Her past medical history was unremarkable; however, her family history was relevant, as three grandparents had diabetes. Blood tests showed elevated haemoglobin A1c (10.7%) and fasting glucose (278 mg/dL), prompting the initiation of insulin therapy. Further tests revealed a normal C-peptide level (2.75 ng/mL) and negative anti-glutamic acid decarboxylase and anti-insulin antibodies. The examination of past medical records revealed pre-diabetes since the age of 13. Genetic testing identified a heterozygous pathogenic variant p.(Glu227Lys) in the KCNJ11 gene. Excellent glycaemic control was achieved upon initiation of gliclazide, leading to the withdrawal of insulin treatment. KCNJ11-MODY is an extremely uncommon subtype of MODY, with only a few reported cases worldwide. This case is important, as it supports the use of sulfonylureas as an effective treatment for KCNJ11-MODY.

Keywords

• diabetes mellitus; MODY; gliclazide; KCNJ11