Poster 20: Case study – Diagnostic pitfalls in young adults with new diabetes.

Morrison D; McGowan R; Jones GC

Dr Deborah Morrison. GP with Special Interest Diabetes, NHS Greater Glasgow & Clyde & Honorary Clinical Lecturer, University of Glasgow;Dr Ruth McGowan. Consultant in Clinical Genetics. West of Scotland Centre for Genomic Medicine & Honorary Clinical Asso
 

We describe a 20-year-old male of Southeast Asian ethnicity presenting with polyuria, polydipsia, random glucose 10.1mmol/l , Hba1c  81mmol/mol, weight 93kgs, BMI 28.8. and no ketonuria. Father type 1 diabetes (aged 20yrs)  and his mother with type 2 diabetes (aged 40yrs). 

Differential diagnosis included type 1 diabetes, type 2 diabetes or Maturity Onset Diabetes of Young (MODY). Three months after diagnosis c-peptide 996pmol/L, GAD/IA2 antibodies negative and HbA1c 67 mmol/ml. HbA1c 53mmol/mol at 6 months post diagnosis on metformin alone.

Next Generation Sequencing was undertaken for a 34 gene MODY panel. Heterogenous variant c.[890A>G];[=] p.(Tyr297Cys) was detected in the Neuronal differentiation 1(NEUROD1) gene which regulates expression of insulin gene. The variant has not been reported in literature either as a pathogenic variant in affected individuals or general population (absent from ClinVar and gnomAD databases).  MRI brain normal and no clinical features of NEUROD1.

As decreased insulin secretion was suspected Gliclazide 80mg B.D was initiated 7 months post-diagnosis with slight improvement in glycemic control. Two months later metformin was stopped with noticeable worsening of glycaemic control (libre glucose management indicator HbA1c 68mmol/mol). After stopping gliclazide and restarting metformin glycaemic control improved - HbA1c 54mmol/mol.

This case demonstrates potential pitfall of MODY testing in ethnicities known to have higher rates of Type 2 Diabetes. Presence of a genetic variant does not automatically confer a diagnosis and clinical correlation is essential.  Clinically Type 2 diabetes is likely diagnosis, with variant an incidental finding.

Discipline: 
Diabetes
Clinical taxonomy: 
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Resource taxonomy: 
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