Genotyping of the lactase-phlorizin hydrolase -13910 polymorphism by LightCycler PCR and implications for the diagnosis of lactose intolerance.
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BACKGROUND: Hypolactasia and lactose intolerance are common conditions worldwide. Hypolactasia seems to be strongly correlated with genotype C/C of the genetic variant C-->T(-13910) upstream of the lactase phlorizin hydrolase (LPH) gene. We developed a rapid genotyping assay for LPH C-->T(-13910) and investigated the relationship of positive lactose breath hydrogen test (LBHT) results suggesting lactose intolerance with LPH C-->T(-13910) genotype. METHODS: Using automated DNA purification on the MagNA Pure LC and real-time PCR on the LightCycler, we examined samples from 220 individuals to estimate genotype frequencies; we then determined LPH C-->T(-13910) genotype in samples from 54 Caucasian patients with a positive LBHT result and symptoms of lactose intolerance. RESULTS: Genotyping of 220 individuals revealed frequencies of 21.4%, 41.8%, and 36.8% for genotypes C/C, C/T, and T/T. Of the patients with positive LBHT results, only 50% had the C/C genotype suggestive of primary adult hypolactasia in our study population. The other patients had various degrees of secondary hypolactasia or symptoms of lactose intolerance. Patients with C/C genotype had a mean (SD) peak H2 increase in the LBHT [108 (58) ppm] that was significantly higher than in patients with the C/T [65 (54) ppm] and T/T [44 (34) ppm] genotypes. CONCLUSIONS: The new real-time PCR assay provides a rapid, labor-saving means for the genotyping of LPH C-->T(-13910). Use of the assay may assist in differentiating patients with primary hypolactasia from those with secondary hypolactasia and lactose intolerance, who may need further clinical examinations to diagnose their underlying primary diseases. (+info)
Mutations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency.
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Congenital lactase deficiency (CLD) is a severe gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. We initially assigned the CLD locus by linkage and linkage disequilibrium on 2q21 in 19 Finnish families. Here we report the molecular background of CLD via characterization of five distinct mutations in the coding region of the lactase (LCT) gene. Twenty-seven patients out of 32 (84%) were homozygous for a nonsense mutation, c.4170T-->A (Y1390X), designated "Fin(major)." Four rare mutations--two that result in a predicted frameshift and early truncation at S1666fsX1722 and S218fsX224 and two point mutations that result in substitutions Q268H and G1363S of the 1,927-aa polypeptide--confirmed the lactase mutations as causative for CLD. These findings facilitate genetic testing in clinical practice and enable genetic counseling for this severe disease. Further, our data demonstrate that, in contrast to common adult-type hypolactasia (lactose intolerance) caused by a variant of the regulatory element, the severe infancy form represents the outcome of mutations affecting the structure of the protein inactivating the enzyme. (+info)
Management and treatment of lactose malabsorption.
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Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world's population, while secondary hypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen causes gastrointestinal symptoms. The condition is known as lactose intolerance. In patients with lactase nonpersistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenous beta-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation. In this review the usefulness of these approaches is discussed and a therapeutic management with a flow chart is proposed. (+info)
Lactose intolerance symptoms assessed by meta-analysis: a grain of truth that leads to exaggeration.
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A meta-analysis was conducted to compare the lactose intolerance symptoms of lactose maldigesters after consuming lactose (as milk, lactose dissolved in water, milk products, or commercial product) with responses after a placebo under masked conditions. An English language MEDLINE search was conducted using the medical subject heading of "lactose intolerance" from 1966 to January 2002. From an initial 1,553 citations, 2 independent reviewers selected 21 studies based on study design (randomized, crossover, blind) and use of an amount of lactose likely to be found in a meal (7-25 g) and a placebo among subjects free of gastrointestinal problems and >4 years old. Mean severity of symptom responses were analyzed as standardized differences, and the presence or absence of a symptom was estimated as pooled incidence differences (ID). For severity of flatulence, the standardized difference was 0.18 (95% confidence interval [CI] -0.16 to +0.52). The CIs for abdominal bloating and pain, degree of diarrhea, frequency of bowel movements per day, and frequency of diarrhea per day also included 0. For abdominal bloating, the ID was 5.9 more people per 100 with symptoms after lactose than placebo (CI -0.07 to +0.19). This same nonsignificant relationship was found for abdominal pain. The ID for diarrhea or loose stools was 0.15 (CI 0.03 to 0.28). Although the incidence of diarrhea was significantly higher, the size of the effect was very small. The results indicate that lactose is not a major cause of symptoms for lactose maldigesters following usual intakes of dairy foods, that is, 1 cup. (+info)
Hydrogen breath test for diagnosis of lactose malabsorption: the importance of timing and the number of breath samples.
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BACKGROUND: The hydrogen breath test (H(2)BT) is the most widely used procedure in the diagnostic workup of lactose malabsorption and lactose intolerance. AIM: To establish whether a simplified two- or three-sample test may reduce time, costs and staff resources without reducing the sensitivity of the procedure. PATIENTS AND METHODS: Data from 1,112 patients (292 men, 820 women) with a positive 4 h, nine-sample H(2)BT were retrospectively analyzed. Patients were stratified according to the degree of lactose malabsorption, the occurrence and type of symptoms. Loss of sensitivity in the procedure was evaluated taking into account two-sample tests (0 min and 120 min or 0 min and 210 min) or three-sample tests (0 min, 120 min and 180 min or 0 min, 120 min and 210 min). RESULTS: Using a two-sample test (0 min and 120 min or 0 min and 210 min) the false-negative rate was 33.4% and 22.7%, respectively. With a three-sample test (0 min, 120 min and 180 min or 0 min, 120 min or 210 min), lactose malabsorption was diagnosed in 91.2% (1,014 of 1,112) patients and in 96.1% (1,068 of 1,112) patients, respectively. Of 594 patients with abdominal symptoms, 158 (26.6%) and 73 (12.2%) would have false-negative results with 0 min and 120 min or 0 min and 210 min two-sample tests, respectively. The three-sample tests, 0 min, 120 min and 180 min or 0 min, 120 min and 210 min, have a false-negative rate of 5.9% and 2.1%, respectively. CONCLUSIONS: A three-sample H(2)BT is time- and cost-sparing without significant loss of sensitivity for the diagnosis both of lactose malabsorption and lactose intolerance. (+info)
Molecularly defined adult-type hypolactasia in school-aged children with a previous history of cow's milk allergy.
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AIM: To assess the role of lactase non-persistence/persistence in school-aged children and their milk-related symptoms. METHODS: The genotypes for the C/T(-13910) variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years (SE = 0.02, 93 boys) participating in a follow-up study for cow's milk allergy. The parents were asked to assess their children's milk consumption and abdominal symptoms. RESULTS: The presence of allergy to cow's milk was not associated with the C/C(-13910) genotype related with a decline of lactase enzyme activity during childhood (lactase non-persistence). The frequency of the C/C(-13910) genotype (16%) was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children (90%) in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C(-13910) genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping (P < 0.004 when compared to the other genotypes). CONCLUSION: Analysis of the C/T(-13910) polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow's milk allergy. (+info)
Lactose intolerance in infants, children, and adolescents.
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The American Academy of Pediatrics Committee on Nutrition presents an updated review of lactose intolerance in infants, children, and adolescents. Differences between primary, secondary, congenital, and developmental lactase deficiency that may result in lactose intolerance are discussed. Children with suspected lactose intolerance can be assessed clinically by dietary lactose elimination or by tests including noninvasive hydrogen breath testing or invasive intestinal biopsy determination of lactase (and other disaccharidase) concentrations. Treatment consists of use of lactase-treated dairy products or oral lactase supplementation, limitation of lactose-containing foods, or dairy elimination. The American Academy of Pediatrics supports use of dairy foods as an important source of calcium for bone mineral health and of other nutrients that facilitate growth in children and adolescents. If dairy products are eliminated, other dietary sources of calcium or calcium supplements need to be provided. (+info)
The crying baby.
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BACKGROUND: Up to 20% of parents report a problem with their infant crying in the first 3 months of life. The majority of babies have no organic cause of crying and most crying subsides by 3-4 months. OBJECTIVE: This article describes the management of persistent crying in the first 3 months of life. DISCUSSION: Management includes exclusion of medical causes and ensuring the baby is adequately rested and fed. Unexplained episodes of crying can be managed by: carrying the baby, going for a walk with baby in the pram, giving baby a deep, warm bath, or playing white noise or environmental sounds to distract the baby from crying. Postnatal depression is common in mothers of crying babies and should be actively screened for and appropriate clinical help offered if required. All families benefit from support including a review appointment and practical help around the home where possible. (+info)