Background & Aims: Many malnourished infants have reduced lactase spec
ific activity in the small intestine. The aim of this study was to tes
t the hypothesis that the hypolactasia of malnourished infants results
from transcriptional suppression of lactase expression. Methods: Biop
sy specimens were studied from two groups of infants: 29 with malnutri
tion and 10 normally nourished controls with normal morphology and lac
tase activity. Results: In malnourished infants, lactase messenger RNA
(mRNA) was reduced to 32% and sucrase to 61% of normal. Lactase and s
ucrase enzyme proteins and activities were lower in malnourished infan
ts, and partial villus atrophy was present. The genotype of adult hypo
lactasia was not present. Conclusions: Because the hypolactasia of mal
nourished children was associated with much lower lactase than sucrase
mRNA abundance and because the epigenetic suppression, which accounte
d for the reduction of sucrase mRNA, was inadequate to explain the gre
ater reduction of lactase mRNA, this study concludes that malnutrition
suppresses lactase gene transcription or mRNA stability in infants. T
he reductions of lactase mRNA, distinct from those found in adults wit
h genetic hypolactasia, explain the low lactase activities commonly fo
und in malnourished infants.