CLINICAL PHARMACOLOGY
Congenital sucrase-isomaltase deficiency (CSID) is a chronic,
autosomal recessive, inherited, phenotypically heterogeneous disease with very
variable enzyme activity. CSID is usually characterized by a complete or almost
complete lack of endogenous sucrase activity, a very marked reduction in
isomaltase activity, a moderate decrease in maltase activity and normal lactase
levels.
Sucrase is naturally produced in the brush border of the small intestine,
primarily the distal duodenum and jejunum. Sucrase hydrolyzes the disaccharide
sucrose into its component monosaccharides, glucose and fructose. Isomaltase
breaks down disaccharides from starch into simple sugars. SUCRAID does not
contain isomaltase.
In the absence of endogenous human sucrase, as in CSID, sucrose is not
metabolized. Unhydrolyzed sucrose and starch are not absorbed from the intestine
and their presence in the intestinal lumen may lead to osmotic retention of
water. This may result in loose stools.
Unabsorbed sucrose in the colon is fermented by bacterial flora to produce
increased amounts of hydrogen, methane and water. As a consequence, excessive
gas, bloating, abdominal cramps, nausea and vomiting may occur.
Chronic malabsorption of disaccharides may result in malnutrition.
Undiagnosed/untreated CSID patients often fail to thrive and fall behind in
their expected growth and development curves. Previously, the treatment of CSID
has required the continual use of a strict sucrose-free diet.
CSID is often difficult to diagnose. Approximately 4% to 10% of pediatric
patients with chronic diarrhea of unknown origin have CSID. Measurement of
expired breath hydrogen under controlled conditions following a sucrose
challenge (a measurement of excess hydrogen excreted in exhalation) in CSID
patients has shown levels as great as 6 times that in normal subjects.
A generally accepted clinical definition of CSID is a condition characterized
by the following: stool pH <6, an increase in breath hydrogen of > 10ppm
when challenged with sucrose after fasting and a negative lactose breath test.
However, because of the difficulties in diagnosing CSID, it may be warranted to
conduct a short therapeutic trial (e.g. one week) to assess response in patients
suspected of having CSID.
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