Possible Etiologies of Sucrase Deficiency

There may be several different underlying causes of deficient sucrase enzyme activity and postprandial gastrointestinal symptoms. Here’s a discussion of how to interpret diagnostic findings from a patient’s medical history, sucrase assay, and an SI genetic test.

Interpretation of Patient History Findings

Likely Genetic or Possibly Genetic Etiology

Patients with a history of gastrointestinal symptoms consistent with reduced sucrase enzyme activity are likely to have an underlying genetic etiology if they are presenting with one or more of the following signs and symptoms:

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 mass index (BMI) that falls below an age-appropriate growth chart curve, or failure to thrive when very young
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 odor
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

Likely Secondary to Other Disorders (Acquired Sucrase Deficiency)

Patients with a history of gastrointestinal symptoms consistent with reduced sucrase enzyme activity may be due to other underlying causes if they are presenting with one or more of the following signs and symptoms:

1. Symptom onset is recent
2. Symptom history is of short duration, particularly when related to a specific mucosal injury or event such as post-infectious irritable bowel syndrome (IBS)
3. There is a clear diagnosis of a primary organic disease or other etiology known to cause sucrase deficiency, such as chemotherapy or celiac disease

NOTE: Secondary (acquired) sucrase deficiency may resolve when the underlying disease or condition is successfully treated.

Interpretation of Sucrase Assay Combined with Small Bowel Pathologic Findings

Patients with a reduced sucrase assay result may or may not have an underlying genetic etiology. Here are the variables one should consider.

Likely Genetic or Possibly Genetic Etiology

Patients with deficient sucrase activity may have an underlying genetic etiology. Interpretation of the sucrase assay and possible etiologies vary by patient age.

Children under 5 years old are likely to have an underlying genetic etiology if they are presenting with one or more of the following findings:

1. Abnormal sucrase activity below the 10^th percentile (<25 U/g);¹ the index of suspicion for a CSID diagnosis should increase when sucrase activity is under the 20^th percentile (<33 U/g) when there are concomitant gastrointestinal signs, symptoms, and a suggestive clinical history
2. Normal small bowel histology, which increases the index of suspicion for a CSID diagnosis. However, an abnormal histology should not be used to rule out CSID²
3. Normal lactase activity (>10 U/g)^3,4

Adults and children over 5 years old are likely to have an underlying genetic etiology if they are presenting with one or more of the following findings:

1. Abnormal sucrase activity below the 10^th percentile (<25 U/g);¹ the index of suspicion for a CSID diagnosis should increase when sucrase activity is under the 20^th percentile (<33 U/g) when there are concomitant gastrointestinal signs, symptoms, and a suggestive clinical history
2. Normal small bowel histology increases the index of suspicion for a CSID diagnosis. However, abnormal histology should not be used to rule out CSID²
3. Normal or abnormal lactase activity^3,4

Likely Secondary to Other Disorders

Patients with deficient sucrase activity may be due to other underlying causes. Here’s how to interpret the findings, by patient age.

Children under 5 years old:

1. Abnormal sucrase activity (<25 U/g)¹
2. Abnormal small bowel histology increases the index of suspicion for other causes, but is not definitive²
3. Abnormal lactase activity (<10 U/g) ^3,4

Adults and children over 5 years old:

1. Abnormal sucrase activity (<25 U/g)¹
2. Abnormal small bowel histology increases the index of suspicion for other causes, but is not definitive²
3. Normal or abnormal lactase activity^3,4

If other causes of the abnormal sucrase activity is suspected, one should conduct further investigations to reach the appropriate diagnosis.

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.⁵

References

1. Quezada-Calvillo R, Robayo-Torres CC, Ao Z, et al. Luminal substrate ‘‘brake’’ on mucosal maltase-glucoamylase activity regulates total rate of starch digestion to glucose. J Pediatr Gastroenterol Nutr. 2007;45(1):32-43. doi:10.1097 MPG.0b013e31804216fc
2. Robayo-Torres CC, Opekun AR, Quezada-Calvillo R, et al. ¹³C-breath tests for sucrose digestion in congenital sucrase isomaltase-deficient and sacrosidase-supplemented patients. J Pediatr Gastroenterol Nutr. 2009;48(4):412-418. doi:10.1097/mpg.0b013e318180cd09
3. Treem WR. Clinical aspects and treatment of congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 2012;55(suppl 2):S7-S13. doi:10.1097/01.mpg.0000421401.57633.9
4. Hackenmueller SA, Grenache DG. Reference intervals for intestinal disaccharidase activities determined from a non-reference population. J Appl Lab Med. 2016;1(2):172-180. doi:10.1373/jalm.2016.020388
5. Sucraid^® [package insert]. Vero Beach, FL: QOL Medical, LLC; 2023.