title: Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies.
abstract: BACKGROUND
  Multiple 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.
  
  
  RESULTS
  A 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 C-starch/breath CO 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. bnichols@bcm.tmc.edu
authors.forename: Buford L
authors.initials: BL
authors.lastname: Nichols
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Avery
authors.forename: Wikrom
authors.initials: W
authors.lastname: Karnsakul
authors.forename: Farook
authors.initials: F
authors.lastname: Jahoor
authors.forename: Partha
authors.initials: P
authors.lastname: Sen
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Swallow
authors.forename: Ursula
authors.initials: U
authors.lastname: Luginbuehl
authors.forename: Dagmar
authors.initials: D
authors.lastname: Hahn
authors.forename: Erwin E
authors.initials: EE
authors.lastname: Sterchi
mesh_terms: D001944:Breath Tests; D002239:Carbohydrate Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007223:Infant; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D043322:Lactase; D008297:Male; D008871:Microvilli / Q000201:enzymology; D013213:Starch / Q000378:metabolism; D013393:Sucrase / Q000172:deficiency* / Q000235:genetics; D000520:alpha-Glucosidases / Q000172:deficiency* / Q000235:genetics; D001616:beta-Galactosidase / Q000172:deficiency* / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D013213:Starch; D043322:Lactase; D000520:alpha-Glucosidases; D001616:beta-Galactosidase; D013393:Sucrase