Lactose intolerance, an intolerance to milk sugar (lactose), can be an inherited or acquired disorder of lactose metabolism. Lactose ingested with food is not sufficiently broken down due to reduced production of the digestive enzyme lactase. As a result, undigested lactose accumulates in the large intestine, where osmotic processes and fermentation in the intestinal flora cause upper abdominal discomfort. The genetic form of lactose intolerance (hereditary, adult-onset form) usually manifests at school age at the earliest and can be detected by a genetic test.
In hereditary lactose intolerance (adult-onset form), the C/T polymorphism in position c.-13910 in the regulatory region of the LCT gene shows a strong association with lactase activity. About 25% of the population of central and northern Europe are homozygous carriers of the inactivating C-allele and are thus affected by this form of lactose intolerance. In southern Europe and other parts of the world, the disruption is much more frequent. In addition to this common polymorphism there are also rarer variants with an association to lactase activity (c.-13907C>G, c.-13913T>C, c.-13914G>A and c.-13915T>G). Inheritance is autosomal recessive, i.e., both alleles must be affected for the intolerance to present phenotypically.
Differential diagnosis should take diseases such as celiac disease or Crohn's disease into account, as they can lead to secondary lactose intolerance. These conditions develop independently of the lactase genotype. In these forms of lactose intolerance, the symptoms are caused by impaired lactase secretion from the damaged intestinal epithelium. A genetic test can be used to distinguish primary lactose intolerance from the secondary form of lactose intolerance. Lactose intolerance in infants and toddlers is not an indication for genetic testing for the hereditary form of lactose intolerance. However, in cases of severe neonatal symptoms (uncontrollable diarrhea, failure to thrive), it may be the congenital form of lactose intolerance caused by pathogenic variants in the LCT gene.
Guandalini 2017, emedicine.medscape.com/article/930971 / Liebert et al. 2017, Hum Genet. 136:1445 / Dzialanski et al. 2016, Clin Biochem 49:248 / Enattah et al. 2002, Nature Genet 30:233 / Sahi 1994, Scand J Gastroenterol 29:7