Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI), also known as
familial hyperinsulinism, pancreatic nesidioblastosis or hyperinsulinemic
hypoglycemia, is a rare genetic disease, that can be inherited in a
dominant or recessive way. It is mainly characterized by the presence of
inappropriately high levels of insulin in parallel with low or very low
glucose levels.
This disease affects newborns and infants and the frequency varies
depending on the population being studied. Estimates have been obtained for
unselected populations, and it is calculated at a frequency of 1 case for
every 40,000 or 50,000 newborns. On the other hand in the Saudi Arabian
population is as frequent as 1:2500 and there is a recent report from
Finland, that also estimates a higher frequency of 1:3200. Some of the
populations that have higher frequency of the disease are small in size and
consanguineous marriages are common. This refers to marrying someone from
your own family, where the probability of having the same good and bad
genes is higher than if you marry someone that comes from a completely
different place. Therefore the frequency of the disease increases.
Like some other diseases with insulin secretory abnormalities, like for
example Diabetes Mellitus, HI (hyperinsulinism) is a very heterogeneous or
variable disease. What this means is that although everyone has high
insulin levels and low glucose levels, the reason why they have it and the
way it shows in the patient is very different.
This is also observed at the molecular level. Currently there are four
different genes that have been identified as responsible for producing HI.
Two that cause a mild or severe form of the disease, inherited in a
recessive or dominant form, and two others, that present only in a mild
dominant form.
HI accounts for approximately 60% of the persistent hypoglycemia in
infancy. From the clinical point of view, infants with this disease can
present convulsions, sleepiness, lethargy, lack of interest in feeding,
breathing difficulty, excessive sweating, abnormal temperature, and blue
appearance, all features associated with hypoglycemia of any cause.
Most of these babies are diagnosed at two different times, depending on the
severity of the disease. The babies with the severe form will be diagnosed
at birth, and most of the ones that have the mild form,
a few weeks or months after birth. This seems to be the general rule, but
there are some exceptions.
A common problem that parents and physicians confront is that the disease
if frequently miss-diagnosed, there are several reasons why a newborn or
infant may have low glucose levels and the correct diagnosis and proper
treatment are very important. The most serious complication is brain damage
and should be avoided at all cost.
The treatments that are currently available are very limited. The main
objective is to maintain a normal level of sugar in the blood. This is done
by using medication (octreotide and/or diazoxide) that will inhibit the
secretion of insulin and in cases where there is no response, surgical
removal of the pancreas becomes necessary.
