The exocrine pancreas is functionally immature at birth. Although
protease function is adequate, lipase and amylase secretion in the
infant approximates 5% to 10% of adult values.
Pancreatic immaturity does not appear to be of major clinical importance,
since there are alternative mechanisms of fat digestion (breast
milk and gastric lipase) and carbohydrate digestion (mucosal glucoamylase
and salivary amylase). Pancreatic dysfunction can be hereditary
Congenital Exocrine Pancreatic Dysfunction
Cystic fibrosis (CF), the most common cause of disturbed pancreatic
function among children, is discussed elsewhere (Chapter 514). Approximately 85% of patients have pancreatic
insufficiency. Regardless of their pancreatic status, all patients
have impaired pancreatic fluid secretion. Patients with CF and pancreatic
sufficiency typically experience milder symptoms and have superior
survival than those with pancreatic insufficiency. Pancreatic function
can be related to specific mutations. For example, patients homozygous
for δF508 have a high likelihood of having pancreatic
insufficiency. Treatment of the pancreatic insufficiency leads to
improvement in absorption, better growth, and normalized stools.
Pancreatic function can be monitored in children with CF with serial
measurements of fecal elastase. Children with pancreatic sufficiency
are at risk for the development of recurrent or chronic pancreatitis.
Certain mutations in the CF gene are associated pancreatic sufficiency,
which appears to place the patient at increased risk for episodes
of pancreatitis and chronic pancreatitis.10
Diamond Syndrome (SDS)
Schwachman Diamond syndrome (SDS) is the second most common cause
of exocrine pancreatic dysfunction in childhood (see also Chapter 432).11 Clinical findings
include malabsorption; short stature with normal linear growth velocity;
skeletal changes, including thoracic dystrophy, clinodactyly, and
metaphyseal dysplasia; bone marrow changes, including neutropenia
(intermittent or persistent), which is virtually universal; and,
less commonly, anemia, thrombocytopenia, and pancytopenia. Almost
a third of patients, predominantly boys, develop myeloproliferative
malignancies. Recurrent infections, due to neutropenia and neutrophil
dysfunction can result in life threatening bacterial infections.
Pancreatic dysfunction usually is less severe than in cystic fibrosis.
Most patients present with signs and symptoms of malabsorption.
The pancreatic lesion is that of acinar cell hypoplasia with intact
function of the pancreatic ducts.
Johanson-Blizzard syndrome is a rare cause of pancreatic acinar
hypoplasia which includes agenesis of the alae nasi, hair anomalies,
deafness, hypothyroidism, genitourinary defects, and delayed development
(Table 417-1).12 Absence of bone
marrow and skeletal abnormalities differentiates it from SDS.
Pearson Pancreatic and
Bone Marrow Syndrome
Pearson syndrome is a rare condition, associated with macrocytic
anemia with varying degrees of neutropenia and thrombocytopenia.3 Erythroid
and myeloid precursors contain peculiar vacuolization and hemosiderosis.
Both acinar and ductal functions are decreased. Unlike Schwachman
Diamond syndrome, there is pancreatic cell atrophy with fibrosis.
Isolated Enzyme Deficiencies
Rare isolated deficiencies of trypsinogen, lipase, colipase,
and combined colipase-lipase have been reported but are poorly documented.
Patients with enterokinase deficiency may appear to have pancreatic insufficiency
because of symptoms of malnutrition, diarrhea, protein malabsorption,
Acquired Pancreatic Exocrine Dysfunction
Exocrine pancreatic disturbance may result from enteropathy,
including celiac disease and postinfectious enteropathy, chronic
pancreatitis, or surgical excision. Enteropathy may cause pancreatic
insufficiency due to a lack of endocrine stimulation of the exocrine pancreas.
Chronic pancreatitis causes pancreatic insufficiency because of
progressive accumulated damage. Surgical excision may result in
pancreatic insufficiency, but more than 95% of the pancreas
must be excised before pancreatic insufficiency occurs. Excision may
be required for hyperinsulinemic hypoglycemia of infancy, pancreatic
tumors, chronic pancreatitis, or following severe trauma to the
Management of Pancreatic Insufficiency
Treatment of pancreatic exocrine insufficiency is with pancreatic
enzymes given with meals (see Chapter 514).
Pancreatic enzymes, particularly lipase, are rapidly denatured by
gastric acid and pepsin. Since pancreatic bicarbonate output is
often reduced, low intestinal pH also reduces enzyme activity. Microencapsulated,
pH-resistant enzyme preparations now available provide protection
from the acidic environment of the stomach. Dissolution of the protective
coating occurs only when microspheres are exposed to a pH above
5.5 to 6.0. Therapy is improved in some patients by inhibiting gastric
acid secretion, thereby increasing duodenal pH. Daily requirements
of enzymes vary considerably from patient to patient. Most patients
require lipase, 1000 to 2000 IU/kg/meal. Despite
pancreatic enzyme supplementation, some patients have persistent
fat malabsorption, requiring supplemental fat soluble vitamins. Enteric-coated
preparations given in excessive quantities (⩾ 5000 IU/kg/dose)
to children with cystic fibrosis have been implicated as a cause
of colonic fibrosis and stricture formation.