Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies

Buford L. Nichols, Stephen E. Avery, Wikrom W Karnsakul, Farook Jahoor, Partha Sen, Dallas M. Swallow, Ursula Luginbuehl, Dagmar Hahn, Erwin E. Sterchi

Research output: Contribution to journalArticle

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. Methods and 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 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. 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.

Original languageEnglish (US)
Pages (from-to)573-579
Number of pages7
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume35
Issue number4
DOIs
StatePublished - Oct 2 2002
Externally publishedYes

Fingerprint

Sucrase
Lactase
glucan 1,4-alpha-glucosidase
sucrose alpha-glucosidase
alpha-Glucosidases
alpha-glucosidase
beta-galactosidase
Oligo-1,6-Glucosidase
Starch
lactose intolerance
Nucleotides
nucleotides
starch
Lactase-Phlorizin Hydrolase
Complementary DNA
Glucan 1,4-alpha-Glucosidase
Amino Acids
enzyme deficiencies
COS Cells
Organ Culture Techniques

Keywords

  • Lactase-phlorizin hydrolase
  • Maltase-glucoamylase
  • Sucrase-isomaltase

ASJC Scopus subject areas

  • Gastroenterology
  • Histology
  • Medicine (miscellaneous)
  • Food Science
  • Pediatrics, Perinatology, and Child Health

Cite this

Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies. / Nichols, Buford L.; Avery, Stephen E.; Karnsakul, Wikrom W; Jahoor, Farook; Sen, Partha; Swallow, Dallas M.; Luginbuehl, Ursula; Hahn, Dagmar; Sterchi, Erwin E.

In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 35, No. 4, 02.10.2002, p. 573-579.

Research output: Contribution to journalArticle

Nichols, Buford L. ; Avery, Stephen E. ; Karnsakul, Wikrom W ; Jahoor, Farook ; Sen, Partha ; Swallow, Dallas M. ; Luginbuehl, Ursula ; Hahn, Dagmar ; Sterchi, Erwin E. / Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies. In: Journal of Pediatric Gastroenterology and Nutrition. 2002 ; Vol. 35, No. 4. pp. 573-579.
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T1 - Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies

AU - Nichols, Buford L.

AU - Avery, Stephen E.

AU - Karnsakul, Wikrom W

AU - Jahoor, Farook

AU - Sen, Partha

AU - Swallow, Dallas M.

AU - Luginbuehl, Ursula

AU - Hahn, Dagmar

AU - Sterchi, Erwin E.

PY - 2002/10/2

Y1 - 2002/10/2

N2 - 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. Methods and 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 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. 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.

AB - 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. Methods and 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 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. 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.

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KW - Maltase-glucoamylase

KW - Sucrase-isomaltase

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