Cow milk protein allergy mimics in infancy

Table 3 Comparison between casein A1–induced intolerance and cow milk protein allergy

Aspect	Casein A1–induced intolerance	CMPA
Mechanism	Non-immune-mediated; caused by the release of BCM-7 during digestion of A1 β-casein	Immune-mediated response to milk proteins (e.g., casein, whey) via IgE or T-cell pathways
Primary trigger	A1 β-casein found in milk from breeds like Holstein and Friesian cows	Any cow’s milk protein, including casein and whey
Symptoms	Gastrointestinal symptoms: Constipation, bloating, abdominal pain. No systemic manifestations	Wide range: Gastrointestinal (vomiting, diarrhea), skin (eczema, rash), respiratory (wheezing), or systemic reactions (anaphylaxis)
Onset	Dose-dependent; occurs after consuming significant amounts of A1 β-casein	It can occur after small amounts of milk protein; onset may be immediate (IgE-mediated) or delayed (non-IgE-mediated)
Age of onset	It is more common in older infants and children and rare in newborns	Typically manifests in infancy, often within the first year of life
Diagnosis	Clinical observation with symptom resolution following a switch to A2 milk. No specific diagnostic tests were available	Based on clinical history, specific IgE tests, skin prick tests, and elimination diets with oral food challenges
Management	Substituting with A2 milk, there is no need for hypoallergenic formulas unless other sensitivities coexist	Avoid all cow’s milk proteins; use extensively hydrolyzed or amino acid-based formulas for infants
Systemic involvement	Absent; symptoms are limited to the gastrointestinal system	Possible, particularly in IgE-mediated cases (e.g., respiratory or skin involvement)
Prognosis	Symptoms resolve with dietary modification, such as switching to A2 milk	Many children outgrow CMPA by 3-5 years; strict dietary management is required until the resolution is reached
Nutritional impact	Minimal if A2 milk or suitable dietary alternatives are included	Risk of nutritional deficiencies if dietary restrictions are not appropriately managed

This comparison underscores the distinct mechanisms, symptoms, and management strategies for casein A1–induced intolerance and cow milk protein allergy. Accurate diagnosis is critical to avoid unnecessary treatments or dietary restrictions and to ensure optimal care. A2 milk: Milk containing only A2 beta-casein. BCM-7: Beta-casomorphin-7; CMPA: Cow milk protein allergy.