Lactase for infantile colic: A systematic review of randomized clinical trials.

Infantile colic is excessive crying for no apparent reason in an otherwise healthy infant. Although its physiopathology is not completely understood, therapies usually target gastrointestinal symptoms. This systematic review of randomized controlled trials (RCTs) analyzes the efficacy of lactase supplementation in infantile colic. PubMed, Embase, and Cochrane were searched for RCTs evaluating lactase supplementation in infants up to 6 months old with infantile colic. Out of six RCTs including 394 patients, three reported a significantly shorter crying time in the lactase group than in the placebo group, while the other three found no significant difference between groups. Of the two studies that performed the hydrogen breath test, only one reported a significant reduction in exhaled hydrogen levels. The pharmacological approach to infantile colic remains debatable, and new studies with standardized diagnostic criteria and outcomes are required to guide lactase supplementation in clinical practice.

Development of a novel SNP assay to detect lactase persistence associated genetic variants.

BACKGROUND: In adulthood the activity of the lactase enzyme is inherited as autosomal dominant form associated to Single nucleotide polymorphisms (SNPs). The present research was aimed to develop a novel genetic method to test lactase non persistence more powerfully. METHODS AND RESULTS: In our study, we selected eight different SNPs that are associated with lactase persistence from Caucasian, Arabian Bedouins, sub-Saharian Africans and Asian populations to set up an approach to detect all the eight different SNPs at the same time in the same sample. This technique is centred on the identification of SNPs with a single nucleotide primer extension method using Sanger sequencing and capillary electrophoresis. CONCLUSIONS: Our method allowed us to check the genotype asset of eight SNPs related to lactase persistence simultaneously and in a very efficient manner. It could be applied to a higher number of SNPs in a single reaction.

Fermented foods and probiotics: An approach to lactose intolerance.

The aim of this review was to present various topics related to lactose intolerance with special attention given to the role of fermented foods and probiotics in alleviating gastrointestinal symptoms. Lactose intolerance is a common digestive problem in which the human body is unable to digest lactose, known as milk sugar. Lactose intolerance can either be hereditary or a consequence of intestinal diseases. Recent work has demonstrated that fermented dairy products and probiotics can modify the metabolic activities of colonic microbiota and may alleviate the symptoms of lactose intolerance. We suggest that, lactose free dairy products could be recommended as alternatives for the alleviation of lactose intolerance and for the promotion of human health and wellness.

Maternal Lactase Polymorphism (rs4988235) Is Associated with Neural Tube Defects in Offspring in the National Birth Defects Prevention Study.

BACKGROUND: The risk of neural tube defect (NTD)-affected pregnancies is reduced with adequate folic acid intake during early pregnancy. However, NTDs have been observed among offspring of women with adequate folic acid intake. Some of these women are possibly not absorbing enough folic acid. Because lactase deficiency can lead to poor nutrient absorption, we hypothesized that lactase-deficient women will be at increased risk of having offspring with NTDs. OBJECTIVE: We examined the association between maternal rs4988235 (a lactase deficiency genetic marker) and NTDs in offspring. METHODS: We conducted a case-control study using data from the National Birth Defects Prevention Study, United States, 1997-2009, restricting to non-Hispanic white (NHW) and Hispanic women. Cases were women with an offspring with an NTD (n = 378 NHW, 207 Hispanic), and controls were women with an offspring without a birth defect (n = 461 NHW, 165 Hispanic). Analyses were conducted separately by race/ethnicity, using logistic regression. Women with the CC genotype were categorized as being lactase deficient. To assess potential effect modification, analyses were stratified by lactose intake, folic acid supplementation, dietary folate, and diet quality. RESULTS: Among NHW women, the odds of being lactase deficient were greater among cases compared with controls (OR: 1.37; 95% CI: 1.02, 1.82). Among Hispanic women, the odds of being lactase deficient were significantly lower among cases compared with controls (OR: 0.50, 95% CI: 0.33, 0.77). The association differed when stratified by lactose intake in NHW women (higher odds among women who consumed ≥12 g lactose/1000 kcal) and by dietary folate in Hispanic women (opposite direction of associations). The association did not differ when stratified by folic acid supplementation or diet quality. CONCLUSIONS: Our findings suggest that maternal lactase deficiency is associated with NTDs in offspring. However, we observed opposite directions of effect by race/ethnicity that could not be definitively explained.

Real-time PCR based detection of the lactase non-persistence associated genetic variant LCT-13910C>T directly from whole blood.

Primary hypolactasia is the main cause of lactose intolerance in adults. It is strongly associated with the single genetic variant LCT-13910C>T, located upstream of the lactase encoding gene. Consequently, analysis of LCT-13910C>T has been recommended as a direct genetic test for the trait. The aim of our study was to develop a TaqMan probe based real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood, circumventing DNA isolation. The LCT-13910C>T variant was determined using the DirectBlood Genotyping PCR Kit (myPOLS Biotec, Konstanz, Germany) together with an in-house TaqMan primer-probe assay. Validity and specificity of the assay was evaluated using EDTA anti-coagulated whole blood samples and corresponding DNA samples. Results from real-time PCR were compared with results obtained by Sanger sequencing from 105 blinded whole blood samples. Validity and specificity of the assay using whole blood were comparable to those using purified genomic DNA as substrate in PCR. Genetic analysis of blood samples were in complete agreement with results obtained by Sanger sequencing. In conclusion, we present a reliable real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood further facilitating diagnosis of primary hypolactasia in symptomatic patients.

Treatment of lactase deficiency in children's obesity with genotype c/c 13910 of lactase gene.

OBJECTIVE: Introduction: Excess lactose in the diet of modern man causes the development of not only lactase deficiency, but it can be a factor that contributes to obesity. The aim: To study associations between obesity and genotype C/C 13910 of lactase gene (LCT) in children, to investigate the effectiveness of treatment using drug exogenous lactase and a low-lactose diet. PATIENTS AND METHODS: Materials and methods: genotyping of lactase gene by real-time polymerase chain reaction, determining the level of lactose maldigestion by hydrogen breath test (HBT), estimating the insulin resistance with the HOMA-IR index in 70 obese children and 40 healthy children 6 - 18 years. Obese children with genotype C/C 13910 and lactose maldigestion (n=40) were randomized in two groups: children from group I (n=20) received an exogenous lactase preparation, and children from group II (n=20) - low-lactose diet. RESULTS: Results: in obese children, the genotype C/C 13910 is 2 times more often than in healthy children. Obese children with genotype C/C 13910 have a significantly higher value of HBT (32.8-39.8 ppm) compared to healthy children (p<0.05), and an increased value of the HOMA-IR index. After treatment, there was a significant decrease in HBT and the HOMA-IR index in the two comparison groups. CONCLUSION: Conclusions: signs of insulin resistance are observed in children with obesity, genotype C/C 13910 and lactose maldigestion. The use of exogenous lactase in the therapy or the administration of a low-lactose diet cause approximately the same decrease in the HOMA-IR index.

Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis.

BACKGROUND: Whether a causal relationship exists between milk intake and reduced risk of fractures is unclear. OBJECTIVES: We tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD). METHODS: We investigated the association between milk intake, LCT-13910 C/T (rs4988235), which is associated with lactase persistence (TT/TC) in Northern Europeans, and hip fractures in three Danish prospective studies (N = 97 811, age ≥20 years). We added meta-analyses of LCT-13910 and fractures and BMD from five published Northern European population studies. RESULTS: In the Danish studies, the adjusted hazard ratio (HR) for hip fracture per one glass per week higher milk intake was 1.00 (95% CI: 0.99-1.01). The per T-allele milk intake was 0.58 (0.49-0.68) glasses per week, but HR was 1.01 (0.94-1.09) for hip fracture. In meta-analyses of Danish studies with published Northern European population studies, the random effects odds ratio for any fracture was 0.86 (0.61-1.21; I2 = 73%) for TT vs. CC and 0.90 (0.68-1.21; I2 = 63%) for TC vs. CC. The standardized mean difference in femoral neck BMD was 0.10 (0.02-0.18; I2 = 0%) g cm-2 for TT vs. CC and 0.06 (-0.04 to 0.17; I2 = 17%) g cm-2 for TC vs. CC. There were no differences in lumbar spine or total hip BMD comparing TT or TC with CC. CONCLUSION: Genetically lifelong lactase persistence with high milk intake was not associated with hip fracture in Danish population-based cohorts. A meta-analysis combining Danish studies with published Northern European population studies also showed that lactase persistence was not associated with fracture risk. Genetic lactase persistence was associated with a higher femoral neck BMD, but not lumbar spine or total hip BMD.

Does primary lactase deficiency reduce bone mineral density in postmenopausal women? A systematic review and meta-analysis.

Postmenopausal osteoporosis is a significant cause of morbidity and mortality. The role of primary lactase deficiency (PLD) in its development is not clear. This meta-analysis showed that PLD is a risk factor for osteoporosis in postmenopausal women. These women need special attention in terms of screening for osteoporosis and its prevention. INTRODUCTION: Postmenopausal osteoporosis is an important predictor of bone fractures. The purpose of the study was to conduct a systematic review and meta-analysis of association of PLD and bone mineral density (BMD) in postmenopausal women. METHODS: The electronic databases PubMed, Scopus, and Web of Science were searched over the course of July 2017 for any date of publication without language limitation. Studies were included in the meta-analysis if the diagnosis of PLD was made by genetic testing or H-2 breath tests and the diagnosis of osteoporosis was made by a modern reliable method for BMD measurement. Two investigators conducted a comprehensive, independent review of all the papers. Five of the studies initially identified met the inclusion criteria. We used MOOSE guidelines for abstracting data and assessing data quality and validity. Meta-analysis was performed using the random effects model. RESULTS: Five case-control studies with 2223 participants and 763 lactase-deficient cases fulfilled the inclusion criteria. Meta-analysis showed a significantly higher bone density Z-score in absorbers (mean difference 0.20, CI (0.14-0.27), P = 0.000), with no significant heterogeneity among the studies. Moreover, the Z-score in the vast majority of the measured sites (femoral head, femoral neck, lumbar spine, radius, and Ward's triangle) was significantly higher in absorbers. There was no significant overall difference in BMD in g/cm2 between absorbers and non-absorbers, but a significantly higher BMD using g/cm2 was observed in absorbers in the total hip site. CONCLUSIONS: Postmenopausal women with PLD had lower Z-scores at most anatomic sites compared to healthy controls.

Intestinal Microbiota in Hirschsprung Disease.

OBJECTIVES: The aim of the study was to characterize the microbiota profiles of patients with Hirschsprung disease (HD) and to evaluate this in relation to postoperative bowel function and the incidence of Hirschsprung-associated enterocolitis (HAEC). METHODS: All patients operated on for HD at our center between 1987 and 2011 were invited to answer questionnaires on bowel function and to participate in a clinical follow-up for laboratory investigations, including fecal DNA extraction, fecal calprotectin (FC), and brush border lactase (LCT) genotyping. The microbiota compositions of patients with HD were compared with those of healthy controls aged between 2 and 7 years. RESULTS: The microbiota composition of eligible patients with HD (n = 34; median age 12 [range, 3-25] years) differed from the healthy controls (n = 141), showing decreased overall microbial richness (P < 0.005). Seventy-seven percent had experienced HAEC. Normal maturation of the intestinal flora was not observed, but patients had a significantly increased abundance of Proteobacteria among other taxa (P < 0.005) resulting in a reduced carbohydrate degradation potential, as predicted by the taxonomic composition. Genetic lactase deficiency was present in 17% and did not correlate with bowel symptoms. No patients reported active HAEC at the time of sampling and FC was within the normal range in all samples. CONCLUSIONS: Patients with HD and HAEC had a significantly altered intestinal microbiome compared to healthy individuals, characterized by a lack of richness and pathologic expansions of taxa, particularly Enterobacteria and Bacilli. Further evaluation is needed to identify whether these observations are intrinsic to HD or secondary to the recurrent use of antibiotics during early childhood.

Lactose Intolerance: Common Misunderstandings.

Lactose intolerance primarily refers to a syndrome having different symptoms upon the consumption of foods containing lactose. It is one of the most common form of food intolerance and occurs when lactase activity is reduced in the brush border of the small bowel mucosa. Individuals may be lactose intolerant to varying degrees, depending on the severity of these symptoms. When lactose is not digested, it can be fermented by gut microbiota leading to symptoms of lactose intolerance that include abdominal pain, bloating, flatulence, and diarrhea with a considerable intraindividual and interindividual variability in the severity of clinical manifestations. These gastrointestinal symptoms could be similar to cow's milk allergy and could be wrongly labeled as symptoms of "milk allergy." There are important differences between lactose intolerance and cow's milk allergy; therefore, a better knowledge of these differences could limit misunderstandings in the diagnostic approach and in the management of these conditions.

Digestive side-effects with teriflunomide: Thoughts on lactose.

INTRODUCTION: Teriflunomide, a novel, orally bioavailable, active metabolite of leflunomide, has anti-inflammatory activity. It is prescribed as a first-line treatment for relapsing-remitting multiple sclerosis (RRMS) at a dose of one 14mg tablet per day. Common adverse reactions observed in placebo-controlled trials with a frequency≥10% and a rate twofold or more than reported with placebo, include digestive disorders. As teriflunomide tablets also contain lactose, the official recommendations are clear about not prescribing this drug to patients with known lactose intolerance and those with rare hereditary problems due to galactose intolerance. METHODS: Our study systematically collected, from our MS clinical practice, all adverse events presenting in the first 100 patients treated with teriflunomide. All of these patients were systematically asked if they were known to have lactose intolerance. RESULTS: None of these 100 patients declared having known, documented lactose intolerance. Yet, after starting teriflunomide, 14 reported mild-to-moderate diarrhea, which resolved within a month, but four of these patients continued to have daily diarrhea (grade 2 WHO classification), prompting us to perform a lactose breath test (LBT) for malabsorption. All four tested positive and were therefore diagnosed with lactose intolerance. Digestive symptoms were resolved with probiotics, and teriflunomide was maintained in three cases; the fourth patient decided, despite the adverse event being resolved, to stop taking teriflunomide. CONCLUSION: In cases of prolonged digestive side-effects after the introduction of teriflunomide, a lactose-malabsorption breath test should be proposed to confirm the culpability or not of an enzymatic defect in the occurrence of adverse events.

Combination of real-time PCR and sequencing to detect multiple clinically relevant genetic variations in the lactase gene.

BACKGROUND: Lactase persistence is an autosomal dominant trait commonly distributed in Europe as well as some parts of east Africa and the Arabian Peninsula. Using real-time PCR to detect the -13910C > T variant common in the European population is a reliable analysis although other variants in the probe-binding site may cause errors in analysis. The aim of this study was to determine the prevalence of the variants in a Danish cohort examined for lactose intolerance as well as to improve the real-time PCR analysis for detection of the different variants. METHODS: We genotyped 3395 routine samples using real-time PCR for the -13910C > T-variant. All consecutive samples identified as -13910CC were sequenced using Sanger Sequencing. Using the SDS software we examined various quality value settings to improve on the genetic analysis. RESULTS: Using real-time PCR resulted in 100% successful genotyping of the -13910C > T variant. By using a quality value of 99% and sequencing the undetermined samples we improved the ability of the assay to identify variants other than -13910C > T. This resulted in a reduction of the diagnostic error rate by a factor of 2.4 while increasing the expenses only 3%. CONCLUSIONS: We conclude that using a quality value of 99% in the SDS software significantly improves the diagnostic efficiency of the real-time PCR assay for detecting variants associated to lactase persistence.

Diagnostic algorithm and peculiarities of monitoring for infants with disorders of the gastrointestinal tract.

INTRODUCTION: The most common medical conditions in infants, which belong to pediatric and gastroenterological disease areas, are functional gastrointestinal disorders, food hypersensitivity and food allergy. First of all, these symptoms can disguise lactase deficiency, cow's milk protein allergy, eosinophilic gastroenteritis, allergic proctocolitis, gastrointestinal manifestations of atopic dermatitis, functional disorders of gastrointestinal and biliary tract, etc. The aim of our study was to develop an algorithm of monitoring for infants with disorders of the gastrointestinal tract and to study the efficacy of probiotic and enzyme replacement therapy. Materials and metods: 47 children aged 1 to 3 years with gastrointestinal and atopic dermatitis symptoms underwent clinical and laboratory examinations. RESULTS: Analysis of additional examination revealed the causes of gastrointestinal disorders, and the following diagnoses were made: 15 children (32 %) had secondary lactase deficiency, 9 children (19 %) had sensitization to cow's milk protein and caseins. Molecular-genetic analysis of С > Т polymorphism at position 13910 of lactase gene (LСT) demonstrated that C/C-13910 genotype was observed in 44.7 % of children, С/Т-13910 heterozygous genotype was found in 36.2 %, and 19.1 % of children had Т/Т-13910 genotype; these were interpreted in conjunction with other clinical criteria for verification of secondary lactase deficiency diagnosis. CONCLUSIONS: Assessment of children over time during their treatment showed that combined therapy using lactase preparation and probiotics contributed to relief of clinical symptoms. All patients had their fecal pH increased (> 5.5), whereas the majority of children demonstrated improvement yet on days 2-3 (i.e., decrease in pain syndrome, flatulency, and stool frequency; restoration of normal stool consistency). Based on the obtained data, we proposed a practical algorithm for verification and monitoring of children with gastrointestinal disorders.

Lactase Non-Persistence Genotyping: Comparison of Two Real-Time PCR Assays and Assessment of Concomitant Fructose/Sorbitol Malabsorption Rates.

BACKGROUND: Genetic testing is a standard technique for the diagnosis of primary adult-type hypolactasia, also referred to as lactase non-persistence. The aim of this study was to compare the lactase gene (LCT) C/T-13910 polymorphism genotyping results of two commercially available real-time (RT)-PCR assays in patients referred to our outpatient clinic for primary lactose malabsorption testing. Furthermore, concomitant conditions of fructose/sorbitol malabsorption were assessed. METHODS: Samples obtained from 100 patients were tested in parallel using the LCT T-13910C ToolSet for Light Cycler (Roche, Rotkreuz, Switzerland) and the LCT-13910C>T RealFast Assay (ViennaLab Diagnostics GmbH, Vienna, Austria). Additionally, patients were also screened for the presence of fructose/sorbitol malabsorption by functional hydrogen (H2)/methane (CH4) breath testing (HMBT). Cohen's Kappa (κ) was used to calculate the agreement between the two genotyping methods. The exact Chi-Square test was performed to compare fructose/sorbitol HMBT with LCT genotyping results. RESULTS: Twenty-one (21.0%) patients had a LCT C/C-13910 genotype suggestive of lactase non-persistence, and 79 (79.0%) patients were identified with either a LCT T/C-13910 or T/T-13910 genotype (i.e., lactase persistence). In all genotype groups, concordance between the two RT-PCR assays was 100%. Cohen's κ demonstrated perfect observed agreement (p < 0.001, κ = 1). Fructose and sorbitol malabsorption was observed in 13/100 (13.0%) and 25/100 (25.0%) individuals, respectively. CONCLUSIONS: Both RT-PCR assays are robust and reliable LCT genotyping tools in a routine clinical setting. Concomitant fructose and/or sorbitol malabsorption should be considered in individuals with suspected lactase-non-persistence. However, standardization of clinical interpretation of laboratory HMBT results is required.

Lactase non-persistence and general patterns of dairy intake in indigenous and mestizo chilean populations.

OBJECTIVES: Lactase persistence (LP) is a genetic trait that has been studied among different countries and ethnic groups. In Latin America, the frequencies of this trait have been shown to vary according to the degree of admixture of the populations. The objective of this study is to better understand the relationship between this genetic trait and dairy intake in a multiethnic context through a synthesis of studies conducted in four regions of Chile. METHODS: Genotypes frequencies for the SNP LCT-13910C>T (rs4988235) and frequency of dairy consumption were obtained from four populations: Polynesians from Easter Island (Rapanui); Amerindians (Mapuche) and Mestizos from the Araucanía region; urban Mestizos from Santiago; and rural Mestizos from the Coquimbo region. Genetic differentiation and association between milk consumption and genotype frequencies were estimated. RESULTS: Genetic differentiation between Native and Mestizo populations was significant; the LP frequency in Mapuche and Rapanui was 10% and 25%, respectively, whereas among the Mestizos, LP frequency was near 40%. Dairy intake was below the nutritional recommendations for the four groups, and extremely below recommendations among the indigenous populations. Association between milk intake and LP was found in Santiago and Rapanui populations. CONCLUSIONS: Although the frequency of LP varies among the populations according to their degree of admixture, dairy consumption was very low across the populations. Given that the association between milk consumption and expected phenotype was found only in two of the populations analyzed, it seems that lactase non-persistence (LNP) is not the only cause for dairy avoidance. Thus, it is suggested that SES and cultural preferences are likely affecting dairy consumption.

Undernourished Children and Milk Lactose.

BACKGROUND: Lactose is an important energy source in young mammals, and in fully breast-fed human infants, it constitutes around 40% of the total daily energy intake. The role of lactose in feeding of undernourished infants and young children is not well described. OBJECTIVE: A narrative review of the potential positive and negative effects of lactose in the treatment of undernourished children. METHODS: Searches were conducted using PUBMED and Web of Science up to July 2015. Relevant references in the retrieved articles were included. RESULTS: Lactose may exhibit several health benefits in young children, including a prebiotic effect on the gut microbiota and a positive effect on mineral absorption. Studies in piglets suggest there might also be a stimulating effect on growth, relative to other carbohydrates. Lactose intolerance is a potential concern for undernourished children. Most undernourished children seem to tolerate the currently recommended (low lactose level) therapeutic foods well. However, a subgroup of severely undernourished children with secondary lactase deficiency due to severe diarrhea or severe enteropathy may benefit from products with even more restricted lactose content. At limited extra costs, lactose or lactose-containing milk ingredients may have beneficial effects if added to food products for undernourished children. CONCLUSIONS: Lactose may be an overlooked beneficial nutrient for young and undernourished children. Research is needed to define the balance between beneficial and detrimental effects of lactose in undernourished children at different ages and with different degrees of diarrhea and intestinal integrity.

[Accuracy of lactase gene C/T-13910 polymorphism and hydrogen breath test in a gastroenterology outpatient clinic: a retrospective study]. / Laktózintolerancia: a laktázgén C/T-13910 polimorfizmusának és a hidrogénkilégzési teszt pontosságának retrospektív kiértékelése gasztroenterológiai szakrendelésen.

INTRODUCTION: Adult type hypolactasia is the most prevalent carbohydrate malabsorption. AIM: To assess the distribution of lactase gene C/T-13910 polymorphism and the accuracy and concordance of a genetic test and H(2) breath test in the diagnosis of adult type hypolactasia. METHOD: 496 patients with symptoms of lactose intolerance were enrolled in a retrospective study who underwent genetic test using TaqMan polymerase chain reaction and H(2) breath test. RESULTS: The prevalence of C/T-13910 genotypes was: CC 48.1%, TC: 40.5%, and TT: 11.4%. When the genetic test was taken as reference, the sensitivity of the breath test was 84.3%, with a specificity of 95.7%, a positive predictive value of 96.7% and negative predictive value of 80.4%. Conversely, the accuracy of genetic test was: sensitivity 96.6%, specificity 80.4%, positive predictive value 84.3% and negative predictive value 95.7%. The concordance value between the two tests (kappa index) was 0.78. The results were discordant in 11.1% of the cases. CONCLUSIONS: In symptomatic patients, the lactase non-persistence genotype CC occurred in almost half of the patients. Both the genetic and the breath tests are sufficiently accurate, with good predictive value and they can be used to set up the diagnosis. Discordant results should be carefully interpreted.

[Lactose intolerance]. / Intolerancia a la lactosa.

The most common problem limiting milk consumption worldwide is lactose intolerance (LI), which is defined as the experience of gastrointestinal symptoms due to the intake of lactose-containing food. When symptoms ensue the intake of milk, the condition is referred as milk intolerance, and it may or may not be due to LI. The most common cause of LI is primary lactase deficiency which occurs in 30% of Mexican adults when one glass of milk is consumed (12-18 g of lactose). LI occurs in less than 15% of adults after the intake of this dose of lactose. Another cause of lactose intolerance is due to secondary lactase deficiency, which occurs because lactase is reduced due to diseases that affect the intestinal mucosa. Lactose intolerance can be eliminated or significantly reduced by elimination or reduction of the intake of milk and milk containing products. Recent studies demonstrate that when ß-casein-A1 contained in milk is hydrolyzed it produces ß-casomorphine-7 which is an opioid associated with milk intolerance.

[Lactose intolerance in neonates with non-infectious diarrhea].

OBJECTIVE: To investigate the development of lactose intolerance in neonates with non-infectious diarrhea and its association with diarrhea, and to evaluate the diagnostic values of fecal pH value and urine galactose determination for neonatal lactase deficiency. METHODS: Seventy hospitalized neonates who developed non-infectious diarrhea between October 2012 and June 2015 were enrolled as the diarrhea group, and 162 hospitalized neonates without non-infectious diarrhea were enrolled as the non-diarrhea group. Test paper was used to determine fecal pH value. The galactose oxidase method was used to detect urine galactose. The neonates with positive galactose oxidase were diagnosed with lactase deficiency, and those with lactase deficiency and diarrhea were diagnosed with lactose intolerance. According to the results of urine galactose detection, 69 neonates in the diarrhea group who underwent urine galactose detection were classified into lactose intolerance group (45 neonates) and lactose tolerance group (24 neonates), and their conditions after treatment were compared between the two groups. The follow-up visits were performed for neonates with diarrhea at 3 months after discharge. RESULTS: Fecal pH value and positive rate of urine galactose (65% vs 54%) showed no significant differences between the diarrhea and non-diarrhea groups (P>0.05). Fecal pH value showed no significant difference between the lactose intolerance and lactose tolerance groups (P>0.05), while the neonates in the lactose intolerance group had a significantly longer time to recovery of defecation than those in the lactose tolerance group (P<0.05). CONCLUSIONS: The incidence of lactase deficiency is high in neonates, and diarrhea due to lactose intolerance tends to occur. Determination of fecal pH value has no significance in the diagnosis of lactose intolerance in neonates with diarrhea.

A novel mutation within the lactase gene (LCT): the first report of congenital lactase deficiency diagnosed in Central Europe.

BACKGROUND: Congenital lactase deficiency is an extremely rare gastrointestinal disorder characterized by neonatal-onset watery diarrhoea and failure to thrive. We present the first genetically confirmed case of congenital lactase deficiency in Central Europe. CASE PRESENTATION: After an uneventful pregnancy and birth, a male newborn of consanguineous parents of Turkish origin presented with watery diarrhoea. On day 17, he was admitted to hospital with weight loss, hypertonic dehydration, and metabolic acidosis. Additionally, the patient showed an elevated calcium concentration in blood and urine as well as nephrocalcinosis. Diarrhoea stopped during intravenous rehydration and when feeding a glucose-, galactose-, and lactose-free formula. Therefore, glucose-galactose-malabsorption was assumed. However, genetic testing of the SGLT1 (SLC5A1) gene was negative and, indeed, feeding maltodextrine did not result in recurrence of diarrhoea. In contrast, lactose feeding immediately caused watery diarrhoea, suggesting congenital lactase deficiency. Genetic testing of the LCT gene revealed homozygosity for a 1-bp deletion in exon 8 (c.3448delT). Because of the nature of the mutation, causing a frame shift and a premature termination of translation, congenital lactase deficiency was confirmed and intestinal biopsies were unnecessary. The patient's general condition improved substantially on a lactose-free diet, including hypercalcaemia, hypercalciuria, and nephrocalcinosis which, however, only disappeared after months. CONCLUSION: This case demonstrates (a) that congenital lactase deficiency should be considered in cases of severe neonatal diarrhoea, (b) that intestinal biopsies can be avoided in typical cases that are confirmed by genetic testing, and