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Pediatric Lactose Intolerance

  • Author: Stefano Guandalini, MD; Chief Editor: Carmen Cuffari, MD  more...
 
Updated: Jul 17, 2015
 

Background

Lactose intolerance in adulthood is very common and is the result of a genetically programmed progressive loss of the activity of the small intestinal enzyme lactase. Some scientists believe that human adult lactase polymorphism evolved in the Neolithic period, after animal milk became available for the nutrition of older children and adults. Expression of the lactase enzyme starts to decline in most persons at age 2 years; almost 4 billion people worldwide have lactose malabsorption. However, symptoms of lactose intolerance rarely develop in people younger than 6 years.

Milk intolerance is more frequently due to milk-protein allergy than primary lactase deficiency. Although transient lactose intolerance may occur during acute gastroenteritis and as part of any process that leads to reduction of the small intestinal absorptive surface (such as untreated celiac disease), it is rarely clinically significant and, when present, can be easily treated with a short course of a lactose-free diet. Diagnosing lactose intolerance based on symptoms is fairly inaccurate; however, self-reported symptoms of lactose intolerance correlate with low calcium intake. Calcium supplementation should accompany any restriction of milk products.

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Pathophysiology

Lactose, a disaccharide unique to mammalian milk, is hydrolyzed into the monosaccharides glucose and galactose at the brush border of enterocytes on the villous tip by the enzyme lactase (a beta-D-galactosidase known as lactase phlorizin hydrolase).

Lactose appears to enhance the absorption of several minerals, including calcium, magnesium, and zinc. The small intestine is a major site of absorption and is illustrated in the image below.

The small intestine is a major site of absorption. The small intestine is a major site of absorption.

It also promotes the colonic growth of Bifidobacterium and is the source of galactose, which is an essential nutrient for the formation of cerebral galactolipids. The gene for lactase is located on chromosome 2. Hypolactasia seems to be strongly correlated with genotype C/C of the genetic variant C-->T(-13910) upstream of the lactase phlorizin hydrolase gene.

The molecular bases of lactose intolerance have been reviewed.[1]

Human and animal studies suggest that numerous modulators result in variable expression of lactase at different ages. Thyroxine may promote the decline in lactase enzyme expression that appears in childhood, whereas hydrocortisone appears to increase lactase levels. Although premature infants have partial lactase deficiency because of intestinal immaturity, enzyme expression can be induced by lactose ingestion. Improvement of lactose digestion in a previously intolerant child or adult is caused by growth of lactose-digesting bacteria rather than an induction in activity of the lactase enzyme because lactase is a noninducible enzyme.

Congenital lactase deficiency is an extremely rare autosomal recessive disorder associated with a complete absence of lactase expression. Childhood-onset and adult-onset lactase deficiency are extremely common and are 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. Persistent lactase activity into adulthood is inherited in an autosomal dominant manner. Acquired lactase deficiency, which is a transient phenomenon by definition, is due to damage of the intestinal mucosa by an infectious, allergic, or inflammatory process and resolves once the disease process is corrected and healing of the intestinal mucosa restores the brush border enzymes.

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Epidemiology

Frequency

United States

Although as many as 20-25% of white US adults are believed to be lactase deficient, the true prevalence of this condition is unknown, as noted in a comprehensive National Institute of Health (NIH) consensus conference on the topic.[2] The prevalence in other racial groups parallels the country of racial origin. Symptomatic individuals represent only about 50% of lactase deficiency cases.

On average, both African Americans and Hispanic Americans consume less than the recommended levels of dairy foods, and perceived or actual lactose intolerance can be a primary reason for limiting or avoiding dairy intake, while true lactose intolerance prevalence is not known in these populations. A recent consensus statement provides an updated overview of the extent of this problem in such populations.[3]

International

Adult-onset lactase deficiency varies widely among countries. Northern Europeans have the lowest prevalence at approximately 5%. Central Europeans have a higher prevalence at approximately 30%, and Southern Europeans have a much higher prevalence at approximately 70%. Hispanic and Jewish populations also have a high prevalence at approximately 70%, while Northern Indians have a much lower prevalence than Southern Indians, at approximately 25% and 65%, respectively. Almost all (90%) Asians and Africans are affected.

Mortality/Morbidity

Usually, very little morbidity is associated with lactase deficiency. Transient lactase deficiency affects a significant number of infants with severe gastroenteritis and diarrhea. Symptoms generally resolve within 5-7 days.

Race

See Frequency.

Sex

No sex differences in the prevalence of adult-type hypolactasia are known.

Age

Lactase activity in the fetal intestine progressively increases through the third trimester and approaches maximum expression at term. Preterm infants have diminished levels of lactase. Few infants born at 28 weeks' gestation have significant intestinal lactase activity, whereas approximately 40% of infants born at 34 weeks' gestation demonstrate significant intestinal lactase activity. The premature neonatal period is the only time in which lactase enzyme production and expression can be induced. Because congenital lactase deficiency is exceedingly rare, diagnoses such as glucose-galactose malabsorption or the much more common milk-protein allergy should be considered in an infant with symptoms of milk or milk-based formula intolerance.

Lactase activity is genetically programmed to decline, beginning after age 2 years. Signs and symptoms usually do not become apparent until after age 6-7 years, and recent studies have actually shown that hypolactasia may begin even after age 20.[4] Symptoms, therefore, may not be apparent until adulthood, depending on dietary lactose intake and rate of decline of intestinal lactase activity. Lactase enzyme activity is highly correlated with age, regardless of symptoms.

Secondary lactase deficiency due to intestinal mucosal injury can appear at any age; however, children younger than 2 years are very susceptible because of many factors, including a high sensitivity of the gut to infectious agents, low reserve because of the small intestinal surface area, and high reliance on milk-based products for nutrition.

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Contributor Information and Disclosures
Author

Stefano Guandalini, MD Founder and Medical Director, Celiac Disease Center, Chief, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago Medical Center; Professor, Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine

Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, North American Society for the Study of Celiac Disease

Disclosure: Received consulting fee from AbbVie for consulting.

Coauthor(s)

Delia M Rivera, MD Assistant Professor, Department of Pediatrics, Division of Infectious Disease and Immunology, University of Miami Leonard M Miller School of Medicine

Delia M Rivera, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Richard E Frye, MD, PhD Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, International Neuropsychological Society, American Academy of Pediatrics

Disclosure: Nothing to disclose.

Stephen M Borowitz, MD Professor of Pediatrics and Public Health Sciences, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Virginia School of Medicine

Stephen M Borowitz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

B UK Li, MD Professor of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin; Attending Gastroenterologist, Director, Cyclic Vomiting Program, Children’s Hospital of Wisconsin

B UK Li, MD is a member of the following medical societies: Alpha Omega Alpha, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching.

Additional Contributors

Eric S Maller, MD 

Eric S Maller, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Society of Transplant Surgeons, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

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The small intestine is a major site of absorption.
 
 
 
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