Monogenic diabetes mellitus in cystic fibrosis.
Hoong-Wei GanJayesh Mahendra BhattLouise DenvirTabitha RandellPooja SachdevPublished in: Archives of disease in childhood (2018)
We present a non-consanguineous family of three siblings who presented with diabetes mellitus (DM), two of whom had genetically confirmed cystic fibrosis (CF), with one pancreatic-sufficient mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (ΔF508/R117H;IVS8-5T). A detailed history revealed family members from three successive generations diagnosed with 'type 1' or 'type 2' diabetes, leading to genetic investigations for monogenic DM. A heterozygous frameshift mutation in the hepatocyte nuclear factor 1 homeobox alpha (HNF1A) gene (c.404delA) was subsequently confirmed in all three siblings, which is known to cause monogenic diabetes and is exquisitely sensitive to sulfonylurea therapy. Following this diagnosis, both siblings with CF and HNF1A monogenic diabetes were started on gliclazide therapy, while their older brother who had been wrongly diagnosed with type 1 diabetes was switched from insulin to gliclazide, all with excellent therapeutic responses.
Keyphrases
- cystic fibrosis
- glycemic control
- type diabetes
- nuclear factor
- pseudomonas aeruginosa
- toll like receptor
- lung function
- genome wide
- copy number
- intellectual disability
- weight loss
- insulin resistance
- cardiovascular disease
- dna methylation
- physical activity
- inflammatory response
- immune response
- single cell
- community dwelling
- skeletal muscle
- autism spectrum disorder
- middle aged
- mesenchymal stem cells
- liver injury
- gene expression