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| 3 | 2004
Klinisk Biokemi i Norden
Genetic testing of adult-type hypolactasia
(primary lactose malabsorption) in clinical practice
Irma Järvelä MD PhD Laboratory of Molecular Genetics, Helsinki University Hospital.
E-post: irma.jarvela@hus.fi
Abstract
Adult-type hypolactasia (lactase
non persistence; primary lactose
malabsorption) is a genetically
determined condition character-
ised by the down-regulation of
the lactase enzyme activity in the
gut wall after weaning. Lactose
malabsorption is a normal condi-
tion. A mutation has occurred during human his-
tory that has made half of the mankind to tolerate
milk (lactose). Lactose malabsorption can cause
symptoms of lactose-intolerance after ingestion of
milk products containing lactose.
A DNA variant, a single nucleotide polymorphism
C/T
–13910
located 13910 bp upstream of the lactase
gene (LCT) at chromosome 2q21-22 has been shown
to associate with lactase persistence/nonpersistence.
Recent functional studies have suggested that this
variant has an enchancer effect over the lactase gene.
Assessment of the C/T
–13910
variant offers a new
diagnostic tool for primary lactose malabsorption
and will replace indirect diagnostic tests due its high-
er sensitivity and convenience to the patients and
lower costs for the laboratory. Clinical interpretation
of the genetic test result still remains a challenge.
Background
Abdominal pain and symptoms are common in
every day clinical practice (1). Primary lactose mal-
absorption (adult-type hypolactasia; lactase nonper-
sistence) has a significant role in recurrent abdomi-
nal pain (2). Lactose malabsorption affects most
of world’s human population and limits the use of
fresh milk due to lactose intolerance (3). Lactose
malabsorption manifests as bloating, flatulence,
diarrhoea and abdominal pain, but about 11-32% of
subjects with low lactase enzyme activity are symp-
tomless (4-5). The occurrence of symptoms depends
on the amount of lactose ingested, the status of
intestine and individual sensitivity. Gastrointestinal
infections and celiac disease reduce the absorption
of lactose. In contrast, up to 57% of patients who
have symptoms from milk containing food, have
normal result in breath hydrogen test (4,6).
The impact of adult-type hypolactasia on abdom-
inal complaints has been difficult to study because
of the variability of clinical symptoms and inac-
curate diagnostic laboratory tests (7). The diagnosis
of adult-type hypolactasia is by definition based on
the measurement of lactase, sucrase and maltase
activities and the lactase and sucrase (L/S) ratio in
intestinal biopsies (8). This invasive technique is not
suitable for primary screening of abdominal com-
plaints. The diagnosis is usually based on the lac-
tose tolerance test (LTT) which specificity has been
reported to range from 77% to 96% and sensitivity
from 76% to 94%. For the breath hydrogen test the
specificity is observed to be 89-100% and sensitiv-
ity 69-100% (8). Use of lactose tolerance test has
been problematic in children due to high rate (up to
30%) of false positive results due to fast absorption
of glucose (9). A question can be raised whether the
test liquid that contains 50g lactose corresponding
a whole liter of milk is justified to give to small
children due to possible pain caused by the large
amount of lactose?
Lactose malabsorption is an evolutionary
phenomenon
Lactose malabsorption is a genetically determined
condition where down regulation of lactase activ-
ity takes place during childhood (3). High lactase
activity in newborns is evolutionally important
enabling breast feeding. Lactase activity will gradu-
ally decrease after weaning, and after that, lactose
malabsorption is a normal phenomenon.
Molecular genetics of lactose malabsorption
Based on family studies, lactose malabsorption is
inherited as an autosomal recessive trait (10). A
mutation has occurred in human history making
nearly half of the world’s population to tolerate
lactose (and milk). This lactase persistence trait has
