Abstract
Hyperinsulinaemic hypoglycaemia (HH) is caused by mutations in the key genes involved in regulation of insulin secretion from the pancreatic β-cells and mutations in
and
are the most common causes of HH. Mutations in
(which encodes the enzyme 3-hydroxyacyl-CoA dehydrogenase) are a rare cause of HH. We report three siblings (21, 9, and 7 years old) from a consanguineous Saudi family with HH due to a homozygous mutation in
. All three siblings presented with HH in the 1st year of life. HH responded well to medical therapy (diazoxide/octreotide) although the 1st sibling suffered neurological damage. The protein load test revealed protein sensitivity in the 21-year-old proband, the oldest reported patient with HH secondary to a
mutation. Genetic analysis revealed a homozygous
splicing mutation (c.133-1G>A) in all three siblings.
mutations can present in later infancy or childhood with severe HH that is usually diazoxide responsive. Severe neurological complications such as epilepsy and developmental delay can be associated with
mutations. This is the 1st report of HH due to
mutation in an adult suggesting that HH could persist into adulthood possibly becoming milder over the years.