Congenital Maltase‐Glucoamylase Deficiency Associated With Lactase and Sucrase Deficiencies

Abstract

ABSTRACTBackgroundMultiple enzyme deficiencies have been reported in some cases of congenital glucoamylase, sucrase, or lactase deficiency. Here we describe such a case and the investigations that we have made to determine the cause of this deficiency.Methods and ResultsA 2.5 month‐old infant, admitted with congenital lactase deficiency, failed to gain weight on a glucose oligomer formula (Nutramigen®). Jejunal mucosal biopsy at 4 and 12 months revealed normal histology with decreased maltase‐glucoamylase, sucrase‐isomaltase, and lactase‐phlorizin hydrolase activities. Testing with a 13C‐starch/breath 13CO2 loading test confirmed proximal starch malabsorption. Sequencing of maltase‐glucoamylase cDNA revealed homozygosity for a nucleotide change (C1673T) in the infant, which causes an amino acid substitution (S542L) 12 amino acids after the N‐terminal catalytic aspartic acid. The introduction of this mutation into “wildtype” N‐terminus maltase‐glucoamylase cDNA was not associated with obvious loss of maltase‐glucoamylase enzyme activities when expressed in COS 1 cells and this amino‐acid change was subsequently found in other people. Sequencing of the promoter region revealed no nucleotide changes. Maltase‐glucoamylase, lactase, and sucrase‐isomaltase were each normally synthesized and processed in organ culture.ConclusionsThe lack of evidence for a causal nucleotide change in the maltase‐glucoamylase gene in this patient, and the concomitant low levels of lactase and sucrase activity, suggest that the depletion of mucosal maltase‐glucoamylase activity and starch digestion was caused by shared, pleiotropic regulatory factors.