Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A

Diana E Stanescu, Nkecha Hughes, Bernard Kaplan, Charles A Stanley, Diva D De León
Journal of Clinical Endocrinology and Metabolism 2012, 97 (10): E2026-30

CONTEXT: Inactivating mutations in HNF1A and HNF4A cause the maturity-onset diabetes of youth (MODY)-3 and MODY1 forms of monogenic diabetes, respectively. Children carrying HNF4A (MODY1) mutations can present in early infancy with macrosomia and diazoxide-responsive hyperinsulinism.

OBJECTIVE: Our objective was to describe three novel cases of hyperinsulinism associated with MODY1 and MODY3 mutations.

RESEARCH DESIGN AND METHODS: Clinical data were obtained from chart review. Gene sequencing was performed on genomic DNA.

RESULTS: Case 1 was diagnosed at 20 months with persistent hyperinsulinemic hypoglycemia and was found to have a novel MODY3 HNF1A mutation, carried by her father who had diabetes. Case 2 was diagnosed with diazoxide-responsive hyperinsulinism at 3 months of age and had complete resolution of hyperinsulinism by 4 yr. She was found to have a novel MODY3 HNF1A missense mutation, also carried by her father. Case 3 presented as a newborn with diazoxide-responsive hyperinsulinism and later developed renal Fanconi syndrome, hypophosphatemic rickets, and hepatic glycogenosis. Although the latter's features suggested Fanconi-Bickel syndrome, sequencing of the SLC2A2 gene was normal. The patient was found to have a known MODY1 mutation in HNF4A. In all cases, the hyperinsulinism improved with age.

CONCLUSIONS: The first two cases demonstrate that mutations in HNF1A (MODY3) can cause hyperinsulinism early in life and diabetes later, similar to the phenotype recently reported for HNF4A (MODY1) mutations. Case 3 indicates that the effects of HNF4A mutations in infancy may extend beyond pancreatic β-cells to produce a disorder similar to glucose transporter 2 deficiency involving both liver glycogen metabolism and renal tubular transport.


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"