Salvatore Auricchio

ACQUIRED MILK INTOLERANCE IN THE ADULT CAUSED BY LACTOSE MALABSORPTION DUE TO A SELECTIVE DEFICIENCY OF INTESTINAL LACTASE ACTIVITY.

C HRONIC diarrhea due to deficient absorption of certain disaccharides has been described recently in infants and children as new inborn errors of metabolism [ 7-71. These syndromes have been variously termed disaccharide malabsorption, hereditary disaccharide intolerance and deficiency of sugar splitting intestinal enzymes. If unrecognized, the course may be steadily downhill, terminating in death of the infant; however, if the noxious sugar is eliminated from the diet, the disorders are essentially benign. Congenital lactose intolerance due to lactose malabsorption, becoming asymptomatic following the institution of a lactose-free (i.e., milkfree) diet, was first described in two siblings by Holzel et al. in 1959 [8] and named “alactasia” [8-701. Since then fourteen such cases have been recorded in the literature [6,8-731. Deficient intestinal lactase activity has been demonstrated recently [ 731. Congenital lactose intolerance associated with lactosuria is probably a distinct and more complex syndrome based on a different pathogenetic mechanism. It was first described by Durand in ‘1958 [ 741, a year before Holzel’s report appeared, as consisting of diarrhea, lactosuria, occasional aminoaciduria, renal acidosis and questionably related autopsy findings in the kidney, liver and central nervous system. Fifteen such patients have been described in the literature [9,74-201, but in none have intestinal enzyme studies been carried out. Twelve of the fifteen infants died despite the institution of a lactose-free diet. Lactose tolerance tests were performed in four infants [9,74,75,78], and the results showed a normal increase in blood reducing substances. This increase may be due to increased absorption of intact lactose, which in turn has a toxic effect on the whole organism, especially the kidneys. At present it appears best to separate the puzzling syndrome described by Durand from that of “benign” lactose intolerance described by Holzel and to regard Durand’s syndrome as a seperate entity rather than a more severe form of Holzel’s entity. Congenital sucrose intolerance due to sucrose malabsorption was first reported in 1960 by Weijers et al. in three children, in one of whom maltose tolerance was also poor [27,77]. Five patients with sucrose intolerance described by Prader et al. in 1961 [22] were later shown to have an additional intolerance to isomaltose and palatinose [23-251 which are split by the same enzyme [26]. A total of thirty-four cases of congenital sucrose intolerance have now been

MULTIPLICITY OF HUMAN INTESTINAL DISACCHARIDASES. I. CHROMATOGRAPHIC SEPARATION OF MALTASES AND OF TWO LACTASES.

Abstract 1. 1. Disaccharidases from normal human intestinal mucosa have been solubilised by “autolysis” and/or papain (EC 3.4.4.10) digestion and have been partially separated by gel filtration on Sephadex G-200. 2. 2. With both types of solubilization used several maltases (maltose glucohydrolases) were found, some of which also have sucrase (sucrose glucohydrolase) of isomaltase (isomaltose glucohydrolase) and palatinase activities. 3. 3. With the same technique the existence of two lactases (lactose galactohydrolases) was demonstrated. Both of them attack cellobiose also. No other cellobiase (cellobiose glucosehydrolase) was found.

Intestinal glycosidase activities in congenitalmalabsorption of disaccbarides

Various disaccharidase activities were determined in the intestinal biopsies of 8 patients with congenital sucrose malabsorption and of 1 patient with congenital lactose malabsorption. In sucrose malabsorption the maltases 3 and 4 (having maltase and sucrase activity) and maltase 5 (having maltase and isomaltase activity) are practically absent while the maltases 1 and 2 (having only maltase activity) are normal. The activity of lactase and trehalase is also normal. In lactose malabsorption all 5 maltases are normal, but the activity of lactase and cellobiase is markedly decreased.

MULTIPLICITY OF HUMAN INTESTINAL DISACCHARIDASES. II. CHARACTERIZATION OF THE INDIVIDUAL MALTASES.

Abstract 1. 1. Human intestinal maltases (maltose glucohydrolases) obtained by solubilization and Sephadex chromatography were examined. Their heat stabilities, substrate specificities, pH-activity curves and Na + activation, as well as their chromatographic behaviour, indicate that 5 maltases are present in normal human intestine. Of these, two hydrolyse sucrose as well. One splits maltose, isomaltose and palatinose. 2. 2. The properties investigated did not apparently change during the solubilization step. 3. 3. The multiplicity of these maltases does not seem to arise during solubilization.