Article Text
Statistics from Altmetric.com
In the past 10 years, several monogenetic abnormalities have been identified in families with congenital intestinal transport defects. Wright and colleagues1 2 described the first, which concerns congenital glucose and galactose malabsorption. Subsequently, altered genes were identified in partial or total loss of nutrient absorption, including cystinuria, lysinuric protein intolerance, Menkes' disease (copper malabsorption), bile salt malabsorption, certain forms of lipid malabsorption, and congenital chloride diarrhoea. Altered genes may also result in decreased secretion (for chloride in cystic fibrosis) or increased absorption (for sodium in Liddle's syndrome or copper in Wilson's disease)—for general review see Scriver and colleagues,3Desjeux,4 and Krawczak and Cooper5(http://www.uwcm.ac.uk/uwcm/mg/hgmd0.html). When considering the rarity of these diseases, we may ask why gastroenterologists should be concerned with these discoveries? My personal answer is that we may gain information in three main areas: (1) the pathophysiology and treatment of these diseases; (2) the use of genetics in gastroenterology; and (3) the genetic control of nutrient absorption. Thus by recognising the entry of genetics into the field of gastroenterology, we may have to adapt to a new way of thinking to fully participate in restoring or maintaining the good health of mankind. In this paper, for the sake of simplicity, only monogenic diseases will be considered.
Relationship between phenotype and genotype
In some diseases the relationship between phenotype and genotype is quite convincing. Glucose and galactose malabsorption (GGM) is a rare congenital disease resulting from a selective defect in the intestinal glucose and galactose/Na+ cotransport system. It is characterised by neonatal onset of severe watery acidic diarrhoea. Children recover if glucose and galactose are withdrawn from the diet. Interestingly, GGM was described by French and Swedish paediatricians when the American biochemist R K Crane was presenting his hypothesis on the glucose-Na+ cotransporter at the luminal membrane of the …