Overview
Definition:
Lactase persistence refers to the continued ability to digest lactose into adulthood, mediated by the enzyme lactase-phlorizin hydrolase (LPH)
The ancestral state is lactase non-persistence (lactase deficiency or adult-type hypolactasia), where lactase expression declines significantly after weaning
Lactase persistence is a common genetic trait, particularly prevalent in populations with a history of dairy farming.
Epidemiology:
Globally, lactase non-persistence affects over two-thirds of the world's population
Prevalence varies geographically, being low in Northern European populations (e.g., <10% in Sweden) and high in East Asian, African, and Native American populations (e.g., >90% in China)
In India, prevalence ranges from 30-70% depending on the region and ethnic group
Lactase persistence is typically inherited in an autosomal dominant manner, linked to specific single nucleotide polymorphisms (SNPs) in the regulatory region of the LCT gene, most commonly -13910*T in Northern Europeans.
Clinical Significance:
Understanding lactase persistence is crucial for diagnosing and managing lactose intolerance, a common cause of gastrointestinal distress in children and adults
Genetic testing can differentiate between primary lactose intolerance (genetic lactase non-persistence) and secondary lactose intolerance (due to intestinal injury)
Genetic counseling is important for families with a history of lactose intolerance or when considering genetic testing, especially in pediatric cases where early diagnosis impacts growth and nutrition.
Diagnostic Approach
History Taking:
Elicit a detailed history of symptoms suggestive of lactose intolerance: abdominal cramps, bloating, flatulence, diarrhea, nausea, and sometimes vomiting, occurring after consumption of dairy products
Ascertain the timing and severity of symptoms relative to milk intake
Inquire about family history of similar symptoms or diagnosed lactose intolerance
Consider age of onset of symptoms and any recent gastrointestinal illnesses that might suggest secondary causes.
Physical Examination:
A thorough abdominal examination is essential
Look for abdominal distension, tenderness, or hyperactive bowel sounds
While the physical exam is often unremarkable in cases of simple lactose intolerance, it is crucial to rule out other causes of similar symptoms
Assess hydration status if diarrhea is prominent.
Investigations:
Lactase persistence can be assessed through several methods
The most definitive is genetic testing (SNP genotyping) for the common regulatory variants, primarily the -13910*T SNP associated with lactase persistence in Northern European populations, and other variants relevant to different ethnicities
Hydrogen breath tests (HBT) measure hydrogen and methane gas exhalation after a lactose load, indicating unabsorbed lactose fermentation
Lactose tolerance tests (LTT) measure blood glucose levels after a lactose load, with a rise indicating effective lactose digestion
Stool acidity tests are less sensitive and specific but can be used in infants.
Differential Diagnosis:
Conditions to consider in the differential diagnosis of lactose intolerance symptoms include irritable bowel syndrome (IBS), celiac disease, inflammatory bowel disease (IBD), bacterial overgrowth (SIBO), infections (e.g., giardiasis), functional abdominal pain, and other food intolerances (e.g., fructose malabsorption)
The presence of alarm symptoms like weight loss, blood in stool, or persistent vomiting warrants further investigation for organic diseases.
Genetic Testing
Indications For Testing:
Genetic testing is indicated for definitive diagnosis of primary lactase non-persistence, especially when HBT or LTT results are equivocal, or to confirm genetic predisposition in individuals with a strong family history
It is also useful in research settings and for understanding population genetics of dairy consumption.
Types Of Genetic Tests:
The most common genetic test involves Single Nucleotide Polymorphism (SNP) genotyping, specifically targeting the MCM6 gene region upstream of the LCT gene, which harbors regulatory elements
Common SNPs tested include -13910*T (for Northern European type persistence), -13907*C, -14010*G, and others depending on ancestry
Direct LCT gene sequencing is rarely needed for diagnosis of common lactase persistence variations.
Interpretation Of Results:
A genotype of CC at the -13910 locus is indicative of lactase non-persistence (ancestral state)
A genotype of CT or TT at -13910 is indicative of lactase persistence
Other SNPs have similar genotype-based interpretations
It is important to correlate genetic results with clinical symptoms and other diagnostic tests, as genetic predisposition does not always equate to symptomatic intolerance.
Counseling And Management
Genetic Counseling:
Genetic counseling should explain the genetic basis of lactase persistence and non-persistence, inheritance patterns, and implications for diet and health
It helps patients understand that lactase non-persistence is a normal genetic variation, not a disease
Discuss the utility of genetic testing, its limitations, and alternative diagnostic methods
For families, discuss implications for family members and potential for future generations.
Dietary Management:
For individuals diagnosed with lactase non-persistence and symptomatic lactose intolerance, dietary management is key
This involves reducing or eliminating lactose-containing foods (milk, cheese, ice cream, yogurt with live cultures may be better tolerated)
Lactose-free milk and dairy products are widely available
Lactase enzyme supplements can be taken before consuming lactose-containing foods
Personalized advice based on symptom severity and tolerance levels is important.
Nutritional Considerations:
Ensure adequate calcium and vitamin D intake, especially if dairy consumption is significantly restricted
Recommend alternative sources such as leafy green vegetables, fortified plant-based milks, and supplements if dietary intake is insufficient
Monitor growth and nutritional status in children with diagnosed lactose intolerance and restricted diets.
Follow Up:
Follow-up is important to assess symptom resolution, adherence to dietary recommendations, and nutritional status
Re-evaluation may be necessary if symptoms persist or if secondary causes are suspected
Education and ongoing support are vital for long-term management.
Age Considerations
Infancy:
True congenital lactase deficiency is extremely rare
Most infants are lactase persistent
Symptoms mimicking lactose intolerance in infants are more often due to feeding issues, cow's milk protein allergy, or immature gut function
Diagnosis of lactose intolerance in infancy requires careful exclusion of other causes.
Childhood:
Secondary lactose intolerance is more common in childhood following gastrointestinal infections (e.g., viral gastroenteritis) or inflammation
Primary lactase non-persistence typically manifests symptoms in late childhood or adolescence as lactase activity naturally declines
Genetic testing can confirm predisposition.
Adolescence And Adulthood:
In developed countries with high rates of lactase persistence, symptomatic lactose intolerance is less common but can still occur due to secondary causes or individual variability
In populations with high prevalence of lactase non-persistence, symptoms often emerge during or after infancy and persist throughout adulthood, influencing dietary habits and cultural practices.
Key Points
Exam Focus:
Understand the genetic basis of lactase persistence and non-persistence, common SNPs (-13910*T), and their geographical distribution
Differentiate between primary (genetic) and secondary lactose intolerance
Know the principles and interpretation of hydrogen breath tests and genetic testing for lactase persistence.
Clinical Pearls:
Always consider secondary causes of lactose intolerance, especially in children with recent GI illness
Yogurt with live active cultures and aged cheeses are often well-tolerated even in individuals with lactase non-persistence due to lower lactose content and bacterial breakdown of lactose
Genetic testing is definitive for primary lactase non-persistence but does not predict symptom severity.
Common Mistakes:
Mistaking normal lactase non-persistence for a disease state
Over-diagnosing lactose intolerance in infants without ruling out other causes like CMPA or feeding issues
Relying solely on genetic testing without clinical correlation
Failing to ensure adequate calcium and vitamin D intake in patients on restricted diets.