Lactase deficiency: classification, etiology, diagnosis, and differences in children

Breast milk is the only possible source of all macro- and micronutrients for newborns. The proteins, fats, and carbohydrates in breast milk are synthesized in such a way as to be most suitable and accessible for digestion in the infant’s gut.

The main carbohydrate in human and other mammalian breast milk is lactose. Lactose is structurally a disaccharide that is broken down in the intestine into two simple sugars: glucose and galactose. They perform the following functions:

• Provide energy value;
• Participate in brain metabolism;
• Aid in the formation of cognitive functions;
• Enhance the absorption of certain minerals;
• Play an important role in colonizing the intestine with beneficial microflora.

The process of digesting lactose is performed by the enzyme lactase, which is synthesized by cells of the small intestine.

In case the infant’s intestine lacks the enzyme for some reason, excess undigested lactose causes digestive disturbances and an inadequate supply of glucose and galactose. This condition is called lactase deficiency.

Since lactose makes up about 80–85% of the carbohydrates in breast milk and adapted milk formulas, the issue of LD is especially relevant for children from 0 to 1 year of age.

Definition and classification of lactase deficiency

Lactase deficiency (hereinafter LD) is a variant of disaccharidase deficiency, primarily involving the disruption of lactose breakdown due to a congenital or acquired deficiency or defect of the enzyme named lactase.

Classification:

• Congenital LD (or congenital alactasia) is an extremely rare genetic disorder characterized by a complete absence of lactase.
• Primary LD is an evolutionarily based, genetically determined decrease in enzyme production with age. Not typical for infants.
• Secondary LD is a reversible form and develops due to damage to the cells of the small intestine (enterocytes) that synthesize lactase.
• Transient (temporary) LD is sometimes highlighted separately; it is typical for premature infants and is associated with the immaturity of their enzyme systems.

Etiology

Congenital LD

Congenital LD is an extremely rare autosomal recessive disorder caused by a mutation in the LCT gene, characterized by a complete absence or sharp decline in lactase enzymatic activity.

In this case, symptoms of LD appear from birth and increase with continued enteral feeding. Only a few dozen cases of this disease have been described worldwide.

Primary LD

Primary or late lactase deficiency, also known as lactose intolerance, is characterized by a gradual decrease in enzyme activity with age.

Since evolutionarily milk is not the main food for an adult, the body reduces the production of the enzyme. Therefore, many adults may experience LD symptoms after consuming dairy products, which resolve after the cessation of lactose intake.

Secondary LD

For the most common form of LD in infants, secondary LD is characterized by prior damage to the mucosal cells of the small intestine and, consequently, reduced synthesis of lactase by enterocytes.

Typically, the primary causes of secondary LD in infants include the following:

• Gastrointestinal infections: intrauterine infection predominantly affecting the intestines, rotavirus infection, salmonellosis, among others;
• Allergic inflammation: allergy to cow’s milk proteins;
• Antibiotic therapy during the neonatal period.

In children older than 1 year, secondary LD is also caused by:

• Crohn’s disease;
• Celiac disease;
• Surgical interventions;
• Chemotherapy;
• Other conditions leading to damage to the mucosa of the small intestine.

Transient LD

This form of LD is only typical for premature babies born before 34–37 weeks of gestation and is associated with the immaturity of the system of synthesis and activation of lactase by enterocytes.

It is a temporary form ending with the natural maturation of the mucosa of the small intestine.

Pathogenesis

Lactase is synthesized by the cells of the mucosa of the small intestine and is located on the brush border membrane of the microvilli of the enterocyte.

Lactase is detectable in the fetus from the 12th week of pregnancy, and its activity grows most during the third trimester.

After the first breastfeeding, lactase activity quickly increases to facilitate the digestion of lactose from breast milk. Approximately five days after the start of enteral feeding, lactose breakdown reaches maximum efficiency.

When lactose enters the intestinal lumen, it is broken down into two simple carbohydrates: glucose and galactose, the intake of which is essential for the infant’s growth and development.

Main functions of glucose:

• Energy: glucose is the main source of energy for maintaining vital functions of the body;
• Maintaining brain function: about 60–70% of all glucose is utilized by the brain;
• Involvement in metabolic processes: it is a component of enzymes and participates in metabolic processes;
• Adaptive: facilitates a smooth transition from intrauterine to extrauterine feeding of the infant.

Main functions of galactose:

• Formation of the central nervous system: it is the main component of the “building material” of neurons, such as galactolipids, sphingolipids, or cerebrosides, and participates in myelination processes;
• Structural: participates in the formation of cellular membranes;
• Energy (secondary): can be metabolized into glucose and used as an energy source;
• Protective: participates in immune processes, forming part of immunoglobulins.

The undigested portion of lactose normally aids in forming a healthy gut microbiota, promoting the growth of bifidobacteria and lactobacilli. These bacteria, in turn, suppress the growth of pathogenic microorganisms and thus perform a protective function.

Any inflammation of the intestinal wall promotes the destruction of enterocytes or damage to their brush border, where lactase is produced. In this case, it is referred to as secondary LD, which is a consequence of the inflammatory process.

Inadequate lactose breakdown results in its excess in the intestine, which is not absorbed, creating high osmotic pressure and causing watery (osmotic) diarrhea.

The gut microbiota ferments lactose into organic acids (lactic and acetic) and gases (hydrogen, methane, carbon dioxide, and hydrogen sulfide), causing excessive flatulence, frothy stools, and a strong acidic smell of feces.

Clinical presentation

The main clinical manifestations of LD include the following:

• Frequent loose stools (osmotic diarrhea);
• Frothy stools;
• Strong acidic smell of stools;
• Abdominal pain, infantile colic;
• Excessive flatulence (increased gas production);
• Increased regurgitation in infants;
• Infant restlessness during feeding;
• Refusal to eat;
• Blood streaks in stools (rare).

Diagnosis of lactase deficiency

In most cases, taking medical history and objective examination data is sufficient to diagnose LD. If the LD diagnosis needs to be confirmed in the laboratory, the following non-invasive tests are performed:

• Stool analysis: determination of carbohydrates in stool—in newborns with LD, more than 1%; in infants older than 6 months, more than 0.6%; determination of pH in stool—in LD, pH is <5.5;
• Hydrogen breath test: determines increased hydrogen concentration in exhaled air.

Additional methods include:

• Genetic testing if congenital LD is suspected;
• Dietary diagnosis involves complete exclusion of lactose from the diet and improvement of the clinical picture against the background of the diet.

Differential diagnosis

In infants, LD should be differentiated with:

• Cow’s milk protein allergy;
• Viral or bacterial enteritis;
• Infantile colic;
• Other disaccharidase deficiencies;
• Cystic fibrosis.

In older children and adults, LD should be differentiated with:

• Irritable bowel syndrome;
• Celiac disease;
• Functional dyspepsia;
• Chronic inflammatory bowel diseases (such as Crohn’s disease and others);
• Parasitic diseases.

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Treatment

The main principle in the treatment of LD is a differentiated approach depending on the type of LD.

The goals of treatment are to optimize lactose digestion while maintaining balanced nutrition and preventing complications.

Treatment of congenital and primary LD involves diet therapy with partial or complete elimination of lactose from the diet. Symptomatic therapy is additionally carried out.

Treatment of secondary LD in infants who are breastfed or fed formula consists of administering a lactase enzyme supplement orally. Such a supplement is added to expressed breast milk or formula before feeding or given to the child orally immediately before each feeding.

In cases where the child is on bottle feeding, it is possible to switch to a low-lactose or lactose-free formula. It is also not recommended to use simethicone medications, often prescribed for infant colic, concurrently with the lactase supplement due to potential decreased effectiveness of LD treatment.

It is important to understand that LD is by no means a reason to stop breastfeeding.

In cases of secondary LD in children older than 1 year, temporary dietary therapy with the exclusion of lactose is relevant; it means refraining from consuming dairy products or temporarily switching to lactose-free dairy products, which are widely available for sale in the modern world.