Original Articles: Gastroenterology
Lactose intolerance is a common problem all over the world, with prevalence rates of 7% to 20% in whites in the United States and Europe (being lowest in those of northern European extraction), 50% in Hispanics, 65% to 75% among Africans, and exceeding 90% in some populations in eastern Asia (1).
Lactose, a disaccharide unique to mammalian milk, is hydrolysed into the monosaccharides glucose and galactose at the brush border of enterocytes on the villous tip by the enzyme lactase (a β-D-galactosidase known as lactase phlorizin hydrolase).
In children, hypolactasia can present in 3 main forms:
- Congenital lactase deficiency, which is an extremely rare autosomal recessive disorder associated with a complete absence of lactase expression
- Childhood-onset lactase deficiency, which is extremely common and inherited in an autosomal recessive manner; the CC genotype of the 13910 C/T polymorphism of the LCT gene is linked to such late-onset primary hypolactasia (2)
- Acquired or secondary lactase deficiency resulting from damage of the intestinal mucosa by an infectious, allergic, or inflammatory insults leading to enteropathy
The symptoms in children are thus related to undigested lactose from the small bowel being fermented by colonic bacteria and ensuing osmotic diarrhoea. This is the basis for diagnostic tests such as lactose tolerance test, breath hydrogen tests, stool pH, and reducing substances. These tests have the advantages of being noninvasive and easy to perform, and paediatricians have had a great deal of experience with them; however, the incidence of false-positive results in lactose tolerance test in children has been reported to be as high as 30% (3). The other tests can have high false-negatives because they rely on the presence of normal colonic flora. Data are scarce on the reliability of these tests in children. The increased usage of antibiotics, in addition, within the community lowers the specificity (4) of the above-mentioned tests.
In adult-type hypolactasia, the criterion standard diagnostic test has been biochemical duodenal lactase (DL) assay (lactase <10 g/U), but this test is invasive and there is a long delay before results are obtained. In adults, a new lactose point-of-care (POC) quick test developed by Sartorius Biohit (Biohit Lactose Intolerance Quick Test [BLIQT]; for endoscopic diagnosis of adult-type hypolactasia Helsinki, Finland) has been in use (5) with sensitivity, specificity, and positive and negative predictive values >95%. At our centre, this test is used as part of the enteropathy screening. The information on the functional capacity of the upper small bowel adds to any histological assessment. The aim of our study was to compare the BLIQT to the criterion standard biochemical DL activity assay in the paediatric population.
Intestinal biopsy specimens of 38 children undergoing upper gastrointestinal endoscopy because of abdominal complaints at Sheffield Children's Hospital between June 2008 and May 2009 were prospectively analysed for the present study. The group consisted of 38 children (mean age 5.45 years; range 0.3–14.8 years; girls, 19).
The biopsies were used for the Lactose Intolerance Quick Test and in biochemical disaccharidase (lactase, trehalase, sucrase, and maltase) assays. Samples were rapidly transported to the laboratories, close to the endoscopy unit, and frozen down in liquid nitrogen.
In the BLIQT, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a colour reaction develops within 20 minutes as a result of hydrolysed lactose (a positive result) in patients with normolactasia (lactase activity >10 U/g protein and lactase/saccharase ratio >0.25), whereas a slight colour change or no reaction (a negative result) develops in patients with hypolactasia.
Quality control of BLIQT was performed before every theatre session to ensure reagents had been stored appropriately and had not deteriorated.
Assay of Intestinal Disaccharidases
The activities of lactase, sucrase, and maltase were determined by a method based on that of Messer and Dahlqvist (6). All of the disaccharidase measurements were carried out at the biochemistry laboratory at the Central Manchester Hospital. We used a cutoff point of 10 U/g protein for lactase activity. Pathologists’ reports were reviewed in every case.
In all of the patients, standard Olympus endoscopes (Olympus, Tokyo, Japan) were used. We further subdivided the group into 2 subgroups:
- Children whose biopsies were done with a larger endoscope (XQ, n = 26) and thus a larger biopsy channel of 2.8 mm
- Children who had a smaller endoscope (XP, n = 12) and thus a smaller biopsy channel of 2.1 mm
The findings are presented in the manner of ability to detect normolactasia (hence demonstrating normal small bowel function).
Findings are presented in Tables 1 and 2. It can be seen that the ability of BLIQT using either a large or small biopsy forcep approximates to a 100% sensitivity in detecting normolactasia and provides 100% concordance with the biochemical assay if it demonstrated hypolactasia. The false-negative rate (on small numbers) is relatively high, giving less confidence that minor degrees of hypolactasia are not detected by a seemingly positive BLIQT.
The sensitivity and specificity of BLIQT on comparing it with DL are extremely high. These results are based on small numbers but tend to support findings in adult studies (5). The ability of the BLIQT in accurately identifying the patients with normolactasia (sensitivity) on comparing it with DL was 100% in both groups. Its ability to accurately identify patients with hypolactasia (specificity) on comparing it with DL was extremely high (86% in XP and 80% in XQ).
The lower specificity in the XQ group perhaps is secondary to the smaller size of the biopsies obtained, and one should consider obtaining 2 biopsies for the BLIQT when using a smaller endoscope.
The low positive predictive value in both groups (57.1% in XP, 50% in XQ) is possibly the result of sample decay in handling. Transportation errors raise the false-negative rate of the biochemical assay. In addition, the existing biochemical reference laboratory values for the DL are based on studies (6,7) done from jejunal biopsies rather than duodenal biopsies. The real positive predictive value of the BLIQT is likely to be much higher. Finally, and more important, it fulfills its role as a POC screening test because its negative predictive value in both subgroups was 100%.
Even though lactose intolerance could result from a number of factors other than the simple lactase activity (eg, gastric emptying rate, intestinal transit time, even individual visceral sensitivity), the clinical value of this test lies in its high sensitivity, negative predictive value, and the result being available immediately. After duodenoscopy, a paediatric gastroenterologist can assure the patient and the family with 100% confidence that the patient has a functionally normal upper small bowel if the BLIQT shows normolactasia. Hypolactasia on the BLIQT would also prompt initiation of diet that is low in lactose until histological assessment is available.
There are no published studies on cost analysis, comparing the BLIQT to hydrogen breath test. In children who are due to have endoscopy and a hydrogen breath test, the costs from a breath test (day care bed costs + nursing input for a few hours) appear on the surface to be more than those from the BLIQT (£18), which can be done as part of the endoscopy. The BLIQT appears to be a reliable POC test for paediatric duodenal hypolactasia.
1. Scrimshaw NS, Murray EB. The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. Am J Clin Nutr
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2. Rasinperä H, Savilahti E, Enattah NS, et al. A genetic test which can be used to diagnose adult-type hypolactasia in children. Gut
3. Krasilnikoff PA, Gudmand-Hoyer E, Moltke HH. Diagnostic value of disaccharide tolerance tests in children. Acta Paediatr Scand
4. Arola H. Diagnosis of hypolactasia and lactose malabsorption. Scand J Gastroenterol Suppl
5. Kuokkanen M, Myllyniemi M, Vauhkonen M, et al. A biopsy-based quick test in the diagnosis of duodenal hypolactasia in upper gastrointestinal endoscopy. Biopsy based quick test for duodenal hypolactasia. Endoscopy
6. Messer M, Dahlqvist A. A one-step ultramicro method for the assay of intestinal disaccharidases. Anal Biochem
7. McMichael HB, Webb J, Dawson AM. Jejunal disaccharidases and some observations on the cause of lactase deficiency. Br Med J
Keywords:Copyright 2012 by ESPGHAN and NASPGHAN
disaccharidase assay; Lactose Intolerance Quick Test; paediatric-type hypolactasia