Disaccharidase Deficiency: An Overlooked Digestive Disorder

Peterson, Powers, MD
Medical Director
Quest Diagnostics Nichols Institute
Valencia, CA
Also by this Author 

Disaccharidases are enzymes the break down complex sugars (like lactose) into simple sugars (like glucose) so that the intestine can absorb the nutrients.  A deficiency of these enzymes in the duodenum results in a range of gastrointestinal symptoms. The common nature of such symptoms may lead to misdiagnosis of the condition as food allergy or intolerance. Dr. Powers Peterson, Medical Director, Quest Diagnostics Nichols Institute, discusses the nature of this disorder and approaches to achieve an accurate diagnosis.

Causes and Symptoms

The major dietary disaccharides are lactose, maltose and sucrose. These are broken down by lactase, maltase and the sucrase-isomaltase complex in the duodenum. “A deficiency in one of these enzymes results in malabsorption of the corresponding sugar, leading to uncomfortable gastrointestinal symptoms,” says Dr. Peterson. “These include bloating, diarrhea, and sometimes borborygmi, more commonly known as stomach rumbling.” While persistent symptoms of this nature, particularly in children, may indicate a disaccharidase deficiency, their common occurrence may lead to an initial misdiagnosis of food allergy or intolerance.

Disaccharidase deficiency may be congenital or acquired. With the exception of adult onset lactase deficiency, hereditary disorders are rare and present at birth. They usually only affect one disaccharide and are irreversible. They include congenital sucrase-isomaltase deficiency, an autosomal recessive disease caused by a mutation in the SI gene,glucose-galactose malabsorption, due to a glucose transporter deficiency, and starch malabsorption due to glucoamylase deficiency.

By far the most common form of disaccharidase disorder is adult-onset lactase deficiency. Lactase activity declines with age and by adulthood the loss of the enzyme leads to lactose intolerance. This is highly prevalent among Asian, African, Native-American and Mediterranean populations.

Acquired disaccharidase deficiency is relatively common, affects all disaccharides, and is associated with intestinal mucosal injury – damage to the small intestinal brush border. “The injury can be due to a genetic abnormality; or auto-immune disorders such as celiac disease or Crohn’s disease; or some other malabsorption syndrome,” explains Dr. Peterson. “It may also be transient. Extended use of antibiotics can be a cause, as can other drugs and toxins, including alcohol and chemotherapy.”

Diagnostic Approaches

Ensuring a timely, accurate diagnosis of disaccharidase deficiency is particularly important in children, given the potentially serious consequences of prolonged symptoms.  The consequences include low levels of body fluids, malnutrition, and a failure to thrive. If a child has persistent, unexplained, gastrointestinal symptoms, the first step in diagnosis is typically diet modification. Foods containing the suspected offending substance are withheld and then re-introduced to assess whether symptoms resolve and then recur. The ubiquitous nature of these substances, however, makes them difficult to eliminate completely, notes Dr. Peterson, while the potential impact on a child’s nutrient intake through their elimination is also a consideration.

If dietary modification is inconclusive or impractical, options for laboratory tests include stool analysis to identify the presence of reducing sugars in feces, a sucrose hydrogen breath test to detect an abnormally high level of hydrogen in the breath of an affected individual after sucrose ingestion, and a sugar tolerance test in which a flat blood serum curve will indicate an abnormality.1

Dr. Peterson notes that the “gold-standard” to achieve a definitive diagnosis is a small bowel biopsy and small bowel enzyme test. “Years of study have shown that the best place to biopsy is the most proximal portion of the intestine, which is just distal to the duodenum,” she says. “A gastroenterologist performs an endoscopy.  During the procedure, at least two biopsies are obtained. One biopsy is sent to a surgical pathologist for analysis of the ‘architecture’ of the intestine, specifically the mucosal pattern.  Is it normal or is there evidence of injury?  For instance, the presence of abrasions indicates an abnormality. The other biopsy is sent for ‘content’ analysis, to determine whether the enzymes are at normal levels. The biopsy tissue is ground up, the protein is measured and a radioimmunoassay is performed to quantify the enzyme level. The results of the two different analyses are then correlated by the patient’s physician.” 

Dr. Peterson stresses the importance of obtaining adequate samples to ensure an accurate test result. “Since you are performing an invasive procedure on a child, it is most critical one obtains an adequate sample first time and avoids the need to repeat the procedure. The challenge is that the samples are extremely small and it’s impossible to know how much protein they contain until they are homogenized for the content assay. If we receive a sample containing only, for example, 0.2 g – and that is insufficient amount of protein -- we cannot know that until the assay has been completed. And that’s too late.” One way physicians ensure they provide a sufficient sample, she says, is by taking an additional biopsy for the content analysis assay, the disaccharidases. This is easily achieved during the endoscopy and there should be no risk of compromising sample integrity.

Once a disaccharidase deficiency is diagnosed,treatment is by dietary modification. This may include the removal of offending sugars or the use of enzymes to aid digestion.


  1. Congenital Sucrase-Isomaltase Deficiency. Genetic and Rare Diseases Information Center. National Institutes of Health. Available at:
    Last reviewed 5/17/2011. Accessed 2/20/2012

Released on Thursday, April 05, 2012