Lactose / fructose intolerance

Clinical information

Primary lactose intolerance is a genetically caused deficiency of the intestinal enzyme lactase, which is responsible for breaking down lactose into glucose and galactose. The fermentation of lactose by bacteria in the ileum and large intestine results in fermentation products, which lead to digestive problems and the typical symptoms such as abdominal pain, nausea, meteorism and diarrhoea. Around 20% of Europeans and almost 100% of the normal population in large parts of Asia and in the south of Africa suffer from primary lactose intolerance.

The two most frequent mutations associated with primary lactose intolerance are the genetic polymorphisms -13910T>C and -22018A>G, which are located in the promoter region of the lactase (LCT) gene. According to the most recent knowledge, humans with the homozygous genotypes C/C_-13910 and G/G_-22018 generally develop symptoms of lactose intolerance, whereas persons with the heterozygous genotypes T/C_-13910 and A/G_-22018 show these symptoms only when they experience stress or suffer from an intestinal infection. Individuals with the genotypes T/T_-13910 and A/A_-22018 are generally lactase persistent and do not show primary lactose intolerance.

Hereditary fructose intolerance (HFI) is a rare autosomal hereditary metabolism disorder caused by a genetic defect of aldolase B, an enzyme of fructose metabolism. Due to the aldolase B deficiency, the toxic intermediate product fructose-1 phosphate (F-1-P) is not broken down any further and accumulates in the body. The symptoms can encompass nausea, vomiting, gastrointestinal complaints, and in the long term liver damage.

The three amino acid substitutes A149P, A174D, N334K and a deletion of 4 nucleotides in exon 4 are the mutations which are most frequently associated with HFI in Europe.  For manifest HFI, both alleles must be affected by one of the mutations. With the homozygous genotype, the same mutation occurs on both alleles (paternal and material heredity). If, however, a heterozygous genotype is present in combination with another mutation, this is referred to as a “compound heterozygous” HFI genotype.

HFI should be differentiated from the much more frequent intestinal fructose intolerance (also called fructose malabsorption; prevalence ~30 %).

Diagnostics

The EUROArray Lactose Intolerance Direct, the EUROArray Fructose Intolerance Direct as well as the combined test EUROArray Lactose/Fructose Intolerance Direct were designed especially for reliable detection of the most important genetic risk factors of primary lactose intolerance and hereditary fructose intolerance and are very easy to perform. With the unique direct procedure, the DNA no longer needs to be isolated. The PCR primers and microarray probes have been carefully selected so that the polymorphisms -13910T>C  and -22018A>G or the mutations A149P, A174D, N334K, del4E4 are clearly identified. Data analysis, data interpretation and electronic archiving are completely automated by means of the EUROArrayScan software. If a mutation is detected, the result issued by the system includes the differentiation between homozygous and heterozygous mutations. The EUROArray test systems described above ensure highest reliability of results especially for rare genotypes. For this purpose, the test systems include highly specific controls that indicate whether the investigated DNA contains further known mutations in direct proximity of the sequence variants being analysed which may affect the binding to the probes and compromise the detection.