Endocrine Abstracts

Introduction: Maturity-Onset Diabetes of the Young (MODY) is a rare cause of Diabetes Mellitus (<5%), resulting from autosomal dominant monogenic defects.

NEUROD1 gene is expressed in pancreatic and neuronal cells, being associated with MODY type 6. Mutations in NEUROD1 gene are reported in 20 families worldwide to date. Heterozygous variant c.616C>A, p.(His206Asn) has never been described.

Case Report: The authors report a case of a 38-year-old woman, with normal BMI, medical history of Hashimoto’s thyroiditis and family history of presumed Type 2 Diabetes (mother and maternal uncles), as well as pancreatic cancer (maternal grandmother). Patient presented with de novo Diabetes: A1C 7.2%, fasting glucose of 146 mg/dl and serum C-peptide 1.8 ng/ml. She did not complain about polydipsia, polyuria, or weight loss. Being a young adult, without classical clinical features of type 1 or type 2 diabetes, and with a strong family history, MODY gene panel was evaluated. An extremely rare mutation on NEUROD1 gene was documented − Heterozygous c.616C>A, p.(His206Asn) variant. Patient’s mothers was also a carrier of the same mutation. Medical Genetics found the mutation pathogenicity doubtful and considered its clinical influence uncertain. The peculiarity of the case led to further analytical investigation: antibodies to GAD65 were positive (113.0 U/ml). Glycaemic control was achieved with a low dose of long-acting insulin (12 units glargine). It has been 4 years since the initial diagnosis and patient is metabolically stable (A1c 6.7%). Serum C-peptide was revaluated: 0.4 ng/ml (with fasting glucose of 98 mg/dl).

The family is being genetically studied at the time of this report.

Conclusion: Current International guidelines consider the presence of antibodies GAD65 an exclusion factor for MODY’s diagnosis. We present a case of a 38 year-old-woman with heterozygous mutation (c616C>A p.(His206Asn)) of the NEUROD1 gene and concomitant antibodies GAD65. Patient had detectable C-peptide at the diagnosis but after 4 years C-peptide is below the normal range. However, glycaemic control was achieved with a single daily dose of long-acting insulin. The most probable diagnosis is a type 1 diabetes with long “honey-moon period” being the genetic mutation in NEUROD1 gene an analytical incidentaloma.

Further genetic evaluation is necessary to define de main cause of metabolic disorder in this patient.