DISORDERS OF THE EXOCRINE PANCREAS

DISORDERS ASSOCIATED WITH PANCREATIC INSUFFICIENCY

Rare in children Includes: Shwachman-Diamond syndrome isolated enzyme deficiencies enterokinase deficiency chronic pancreatitis protein-calorie malnutrition

1. Cystic Fibrosis
most common lethal genetic disease and the most common cause of malabsorption among white American or European children by the end of 1 yr.: 8590% - develop pancreatic insufficiency, which, if untreated, can lead to malnutrition treatment of the associated pancreatic insufficiency leads to:
improvement in absorption better growth, and normalized stools

 Pancreatic function - can be monitored with serial measurements of fecal elastase Certain mutations in the cystic fibrosis gene have been associated with idiopathic chronic pancreatitis

2. Shwachman-Diamond Syndrome (SDS)

autosomal recessive syndrome (1/20,000 births) Presents with: pancreatic insufficiency; neutropenia, which may be cyclic neutrophil chemotaxis defects; metaphyseal dysostosis; failure to thrive; and short stature Some: have liver or kidney involvement or learning difficulty

 In infancy: poor growth and greasy, foul-smelling stools that are characteristic of malabsorption may be seen normal sweat chloride levels, lack of the cystic fibrosis gene, characteristic metaphyseal lesions, and fatty pancreas on CT examination
Despite adequate pancreatic replacement therapy, poor growth frequently continues Pancreatic insufficiency transient, and steatorrhea may spontaneously improve with age

 Recurrent pyogenic infections otitis media, pneumonia, osteomyelitis, dermatitis, sepsis are common and are a frequent cause of death
Thrombocytopenia is found in 70% of patients and anemia in 50%. 33%- Development of a myelodysplastic syndrome 24%- transformation to acute myeloid leukemia

SDS gene- found in chromosome 7

 Pathologically: pancreatic acini are replaced by fat with little fibrosis Islet cells and ducts are normal The fatty pancreas has a characteristic hypodense appearance on CT and MRI scans

3. Pearson Syndrome
sporadic mitochondrial DNA mutation affecting oxidative phosphorylation manifests in infants with severe macrocytic anemia and variable thrombocytopenia The bone marrow demonstrates vacuoles in erythroid and myeloid precursors as well as ringed sideroblasts pancreatic insufficiency contributes to growth failure may develop diabetes mellitus (Kearns-Sayre, chronic progressive external ophthalmoplegia, diabetes with deafness syndromes) Mitochondrial DNA mutations are transmitted through maternal inheritance to both sexes or are sporadic

4. Isolated Enzyme Deficiencies

a. Enterokinase deficiency causes pancreatic insufficiency because pancreatic proteases remain inactive b. Enterokinase or trypsinogen manifest with failure to thrive, hypoproteinemia, and edema

typically developmental and resolves by age 23 yr

SYNDROMES ASSOCIATED WITH PANCREATIC INSUFFICIENCY

Rare causes: a. Pancreatic agenesis b. Johanson-Blizzard syndrome pancreatic insufficiency, deafness low birthweight, microcephaly, midline ectodermal scalp defects, psychomotor retardation, hypothyroidism, dwarfism, absent permanent teeth, and aplasia of the alae nasae c. congenital pancreatic hypoplasia d. congenital rubella

 Some children with both syndromic (Alagille) and nonsyndromic paucity of intrahepatic bile ducts also have pancreatic insufficiency associated with their liver disease May be seen in patients with duodenal atresia and stenosis May be seen in infant with familial or nonfamilial hyperinsulinemic hypoglycemia (formerly called nesidioblastosis) who requires 95100% pancreatectomy to control hypoglycemia

Treatment of Pancreatic Insufficiency

ORAL ENZYME REPLACEMENT

usually corrects creatorrhea Steatorrhea is difficult to correct completely due to: variability of lipase activity in different commercial preparations inadequate dosage incorrect timing of doses lipase inactivation by gastric acid chymotrypsin in the enzyme preparation digests and thus inactivates lipase

Preparations Most Widely Used: Pancrease, Creon, Ultrase, and Panceacarb enteric-coated preparations that resist gastric acid inactivation Generic enzyme preparations- less effective and should be avoided Dosage: depends on the amount of food eaten established by trial and error estimated from the lipase requirement of 5001,500 IU/kg/meal adequate dose is one that is followed by the return of the stools to normal fat content, size, color, and odor

 Enzyme replacement should be given at the beginning of and with the meal Tablets should be chewed powder and granules can be mixed with a small quantity of food must also be given with snacks Increasing enzyme supplements beyond the recommended dose does not improve absorption, may retard growth, and may cause fibrosing colonopathy

 H2-receptor antagonist or a proton pump inhibitor gastric acid neutralizers use when adequate fat absorption is not achieved decreases enzyme inactivation by gastric acid and improves delivery of lipase into the intestine enteric-coated preparations- protects lipase from acid inactivation.

Untoward effects occurs 712 mo after high-dose pancreatic supplement therapy (ranging from 6,500 to 58,000 IU lipase/kg/meal). allergic reactions increased uric acid levels and kidney stones Fibrosing colonopathy- colonic fibrosis and strictures

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