Background: The prevalence of maturity-onset diabetes of the young (MODY) in Saudi population remains unknown and data on molecular etiology of this condition is limited.
Objective and hypotheses: The present study was undertaken to elucidate the clinical and molecular characteristics of a Saudi family with MODY1.
Method: A 12-year-old female presented to us with symptoms suggestive of diabetes. Investigations revealed hyperglycemia, glycosuria, and ketonuria with no acidosis. Pancreatic antibodies were negative. She responded well to s.c. insulin. Her family history revealed that two of her siblings were diagnosed with type 1 diabetes (T1DM) while her father and mother have T2DM. In view of this strong family history, the possibility of monogenic diabetes was raised, namely hepatocyte nuclear factor 1α and 4α genes (HNF4α and HNFα1). Accordingly, genomic DNA was isolated from peripheral blood lymphocytes of the eight members of this family, PCR was carried out, and sequencing of the whole HNF1α and HNF4α gene was done.
Results: DNA study of the proband revealed heterozygous substitution at position-nt5 in intron 1 of the HNF4α gene. This mutation was identified in other five members of the family.
Conclusion: This report highlights the importance of considering MODY in any individual diagnosed with either T1DM or T2DM, who have atypical features for these polygenic disorders. The red flags for prediction of monogenic diabetes include strong family history of diabetes and early presentation in young age group especially when ketoacidosis, anti-islet antibodies, and obesity are not features. Confirming this diagnosis at molecular level facilitates management, improves outcome and provides effective genetic counselling.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology