CHOP Article Highlights Three Novel Cases of HNF HI

Published on in HI Hope

With the highest patient volume in the United States, it follows that CHOP’s Congenital Hyperinsulinism Center sees more children with rarer types of hyperinsulinism (HI), too. That led CHOP physician-scientists to write about three novel cases of HI due to mutations in the MODY (maturity-onset diabetes of youth) genes, HNF1A and HNF4A. Two of the cases are the first to report HNF1A mutations as a cause of congenital HI.

In case 1, the child showed no signs of hypoglycemia until she was weaned from breastfeeding at 20 months old, except for a 72-hour episode after birth that resolved itself. She was diagnosed with HI and treated with diazoxide for two months. By age 6, she showed no signs of HI. Her father had adult-onset diabetes, and his DNA test showed a mutation in the HNF1A gene.

In case 2, a 3-month-old female had a hypoglycemic seizure and was diagnosed with HI. Diazoxide controlled her HI until she no longer needed it at 3 years old. Her father, 30, had a mutation in the HNF1A gene, but had not yet developed diabetes.

In case 3, a female infant developed severe hypoglycemia hours after birth. She was treated with dextrose for a week, then released. Three weeks later, after a hypoglycemic episode, she was diagnosed with HI. She was successfully treated with diazoxide, with lower and lower doses, until age 4, when the HI resolved. She also had renal abnormalities compatible with renal Fanconi syndrome. Genetic testing was negative for the typical HI genes and the gene responsible for Fanconi-Bickel syndrome, but she showed a novel mutation in HNF4A. There is no family history of diabetes or Fanconi syndrome.

It is not known how the same mutations can result in HI early in life and diabetes later. Recognizing the cause of hyperinsulinism in these cases changes the prognosis and management. Knowing diabetes is a strong possibility later in life raises the chance of early diagnosis and management.