CSID- Congenital

Sucrase-Isomaltase
Deficiency
- MVS HARDHIK

 What is CSID
It is a rare genetic disorder affecting the digestive
function of sucrase and isomaltase enzymes in the small
intestine.

A decrease or absence of activity of these enzymes, required for the

digestion of dietary sucrose and starch, is characterised by varying
degrees of chronic diarrhea, abdominal pain, gas, and bloating in
those who are affected.

Congenital Sucrase-Isomaltase Deficiency is also referred to as

Genetic Sucrase-Isomaltase Deficiency (GSID), sucrose intolerance,
or disaccharide intolerance.

It is a rare autosomal recessive disorder. Shows dysfunctional SI

(sucrose-isomaltase) gene mutations.

 THE ETIOLOGY OF CSID

Sucrase-isomaltase consists of two integral carbohydrate-digesting
glycoproteins expressed in small intestinal enterocytes and
transported to the cell membranes of brush border microvilli.

Absent or diminished sucrase-isomaltase enzyme activity allows

undigested sugars to collect in the lumen of the small intestine and
pass into the large intestine, causing colonic fermentation and acidic,
watery diarrhea via osmosis.

If left untreated, the disease can lead to accelerated motility and broad
malabsorption of all nutrients (not just carbohydrates) resulting in
weight loss, low body mass index, dehydration, metabolic acidosis,
hypercalcemia, failure to thrive, and developmental delay.

LIKELY GENETIC or POSSIBLY GENETIC ETIOLOGY

1. Very long-term symptom duration (since childhood or for many

years)
2. Frequent and postprandial symptoms with reports of carbohydrate
avoidance or intolerance (particularly sugary sweets or starches,
such as potatoes, pasta, or bread)
3. Chronic and frequent diarrhea and/or loose stools with a high
daily bowel movement frequency, gas/bloating and abdominal
pain, and possible nausea and/or dyspepsia
4. Low body weight (very thin phenotype or low BMI relative to
age-appropriate values)
5. Long history of diagnostic workups with multiple
gastroenterologists for unusual, but similarly presenting,
pathologies such as cholecystitis, celiac disease, cystic fibrosis,
and bile acid malabsorption
6. Close family history of similar signs and symptoms, especially
parents, children, or siblings

7. Reports of strong stool odour.

8. In children, symptoms often start after weaning coincident with
increased consumption of dietary carbohydrates
9. In children, symptoms may manifest as severe acidic diarrhea,
with many diaper changes per day, and severe diaper rash or
excoriated buttocks.

 SUMMARY

A CSID diagnosis can be made when signs and symptoms indicate

long-term moderate to severe carbohydrate maldigestion, confirmed
by low sucrase activity and a clear response to therapy.

The prescription sucrase enzyme replacement, Sucraid® (sacrosidase)

Oral Solution, has been studied and approved for genetically
determined sucrase deficiency.

 WHO IS AFFECTED BY CSID ?

Males and females are affected equally by CSID.

Children may present with symptoms that are more severe because
they have a shorter small intestine.

Patients who have CSID with moderate enzyme deficiency may not
have a classic presentation of severe osmotic diarrhea in early
childhood and may not be diagnosed until they are adolescents or
adult.

CSID SYMPTOMS

In patients with this disease, reduced or absence of SI enzyme

activity results in the presence of undigested dietary sugars and
starches in the lumen of the small intestine and the colon.

This accelerates the transit time time if the entire meal through the
small intestine.

Colonic microflora then metabolise the unabsorbed substrates.

Sucrose is the most clinically significant substrate because it
results in rapid fermentation, which releases methane, hydrogen,

 and carbon dioxide gases and causes abdominal pain, flatulence,

bloating, and abdominal distension.

CHRONIC SYMPTOMS OF CSID. SIGNS and SYMPTOMS

• abdominal pain, cramps Frequent : multiple events per

• abdominal distension. day , multiple days per week
• flatulence. (gas, bloating, diarrhea,
• excoriated buttocks, diaper abdominal pain, nausea, and
rash. vomiting)
• nausea and vomiting. Lifelong : truly chronic patients
• dyspepsia. Postprandial : symptoms after
• failure to thrive. eating.
• weight loss. Other signs : high diarrhea freq
FH : likely relatives with
chronic “IBS-D like” symptom
Urgent need for bathroom.

While most individuals affected by CSID present with classic

symptoms, many are given a nonspecific diagnosis of toddler’s
diarrhea as infants and young children.

Many patients who achieve normal growth are not diagnosed with
CSID until they are between the ages of 2 to 8 years, or even later
in adolescence or adulthood.

DIET FAILURES CAN HELP IDENTIFY CSID PATIENTS

Subset of gas/bloating/diarrhea patients who also report avoidance

of sucrose and starch food items.

Low-FODMAP (fermentable oligo di- mono- saccharides and

polyols ; They are short chain carbohydrates that are poorly
absorbed in the small intestine, and are prone to absorb water
and ferment in the colon ) diet (does not exclude sucrose)

Gluten-free diet ( does not exclude sucrose or starch).

 HOW COMMON IS SUCRASE

DEFICIENCY?

DIAGNOSTIC TESTS

Sucrase assay via Small Bowel Biopsy and Disaccharidase

Assay - THE GOLD STANDARD

Disaccharidase Assay
Measures activity of 4 enzymes: lactase, sucrase, Maltese,
palatinase (isomaltase).
2-3 extra distal duodenal biopsies (best near ampulla of Vater).
Freeze and dry ice ship to speciality lab (not path lab)

Disaccharidase Assay can be broadly helpful to:

Help rule in/out celiac disease or lactase intolerance.
Asses small bowel health.

 Carbon-13 sucrose breath test (13C SBT)

This is a noninvasive test that is relatively short in duration and can be

administered by the patient in their home.

Sucrase activity is considered abnormal when, after consuming a 20-g

sucrose solution, a cumulative [13C] CO2 exhalation over 90 minutes
is below the 10th percentile, which is <3.9% for men and <5.2% for
women.

Sucrose hydrogen-methane breath test

This is another non invasive test that can be done at home.

Here the patient consumes 50 g sucrose.

Sucrase deficient patients will likely have gastrointestinal symptoms

during or shortly after the test due to the 50-g sucrose load.

4-4-4 Oral sucrose challenge test

This is another non invasive test.

A fasting patient simply drinks a well-dissolved solution of 4

tablespoons of table sugar in a 4-ounce glass of water.

If sucrase activity is diminished or absent, the patient will experience

the gastrointestinal symptoms associated with colonic fermentation of
the sucrose, such as gas, bloating, distention, and diarrhea. Moderate
or severe symptoms will appear in 4 hours.

Sucrose Challenge Symptoms Test

Step1 : stir 4 tablespoons of ordinary table sugar into a 4-ounces

glass of water. Mix until sugar is completely dissolved.

Step2 : drink it on an empty stomach.

Step3 : see if symptoms such as bloating, gas, diarrhea occur

during the next 4-8 hours; such symptoms suggest that you might
have sucrose intolerance.

TREATMENTS FOR CSID

• Severe diet restriction

• Sucraid® (sacrosidase) Oral Solution (ENZYME

REPLACEMENT THERAPY)

• Sucraid with moderate diet restriction

Enzyme replacement therapy

Sucraid is the only FDA-approved therapy for the treatment of

genetically determined sucrase deficiency

Sucraid does not provide specific replacement therapy for deficient

starch digestion.9 Therefore, restricting starch in the diet is usually
necessary in patients with CSID.

Proper dosing is essential for Sucraid to be effective. The proper

dosage is 1 mL or 2 mL (one or two full measuring scoops) with each
meal or snack. Each full measuring scoop equals 1 mL. The proper
dose of Sucraid by body weight is:

 • For patients weighing up to 33 lb (15 kg): 1 mL (one full

measuring scoop)
• For patients weighing more than 33 lb (15 kg): 2 mL (two full
measuring scoops).

The low-FODMAP (fermentable oligo di- mono- saccharides and

polyols ; They are short chain carbohydrates that are poorly absorbed
in the small intestine, and are prone to absorb water and ferment in the
colon. ) diet is not recommended for patients with CSID, although it is
a standard diet for irritable small bowel syndrome.