This extremely rare condition results in early-onset
insulin-dependent diabetes mellitus (IDDM) and exocrine pancreatic
Congenital Pancreatic Hypoplasia.
Approximately 10 cases of pancreatic agenesis have been
Autosomal recessive transmission. The genetic
defect results from a mutation of the human insulin promoter factor-1 (IPF1)
gene, which is located on 13q12.1.
The homeodomain protein IPF1 is critical for the
development of the pancreas and is a key factor in the regulation of the
insulin gene in the beta cells of the endocrine pancreas. Targeted
disruption of the gene encoding IPF1 results in failure of the pancreas
to develop (pancreatic agenesis). Intrauterine growth retardation appears to
be related to the fact that insulin is a major intrauterine growth factor.
Exclude Mucoviscidosis, which is the most common
cause of exocrine pancreatic insufficiency in childhood. The findings of
intrauterine growth retardation (insulin is a known prenatal growth factor
that does not cross the placenta in clinically significant amounts) and
early-onset IDDM combined with clinical and biochemical evidence of
pancreatic exocrine insufficiency may fit the diagnosis of congenital
pancreatic aplasia/hypoplasia. In contrast to cases with absence of islets
of Langerhans or complete pancreatic aplasia, serum levels of C peptide and
glucagon may be measurable in partial aplasia. The diagnosis of pancreatic
agenesis is difficult to establish in the newborn period. The size of the
infant makes use of endoscopic retrograde cholangiopancreatography
hazardous, and normal newborn comparisons are not well established for
radiologic examinations. Clues pointing to the diagnosis include
intrauterine growth retardation, failure to thrive, persistent
hyperglycemia, polyuria, glycosuria, and steatorrhea.
Intrauterine growth retardation with early-onset
IDDM is typical. Affected infants may develop profound polydipsia and
polyuria because of increased osmotic load resulting in rapidly progressing
dehydration. Hyperglycemia in newborns can be associated with an increased
incidence of intraventricular hemorrhage. Overly aggressive insulin therapy
can result in hypoglycemia with adverse neurologic sequelae. Ketoacidosis is
a rare finding in these patients, and some researchers hypothesized this
finding results from the lack of hyperglucagonemia. Despite appropriate
insulin and exocrine pancreas hormone replacement therapy, some patients
fail to gain weight. Serum insulin levels may be very low or undetectable.
Limited joint mobility has been reported in some patients.
Admit the patient 24 to 48 hours
preoperatively to optimize insulin therapy and try to keep the blood glucose
levels slightly higher (i.e., 5-12 mmol/liter) than generally accepted for
older children. These patients should be booked at the beginning of the
operating list. Different treatment options are available for the management of
IDDM. We recommend the treatment you commonly use and with which you are
familiar. One regimen consists of omitting the morning dose of insulin,
starting an intravenous glucose-insulin infusion (either separately or
mixed), and adding potassium as required. Preoperative laboratory
investigations should include a 24-hour serum glucose profile, glycosylated
hemoglobin or fructosamine, fasting blood glucose level, complete blood
count, and serum concentrations ...