Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies.
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.
Nichols
Buford L
BL
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. bnichols@bcm.tmc.edu
Avery
Stephen E
SE
Karnsakul
Wikrom
W
Jahoor
Farook
F
Sen
Partha
P
Swallow
Dallas M
DM
Luginbuehl
Ursula
U
Hahn
Dagmar
D
Sterchi
Erwin E
EE
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
D018076:DNA, Complementary; D013213:Starch; D043322:Lactase; D000520:alpha-Glucosidases; D001616:beta-Galactosidase; D013393:Sucrase