(Received October 16, 1972; revision accepted for publication January 8, 1973.)
Drs. Akesode and Hoffman are residents in pediatrics.
ADDRESS FOR REPRINTS: (F.L. ) Department of Pediatrics, North Shore Hospital, Manhasset, Long
Island, New York 11030.
PEDIATRICS, Vol. 51, No. 5, May 1973
891
TRANSIENT
MONOSACCHARIDE
INTOLERANCE
IN A
NEWBORN
INFANT
Fatiu Akesode, Fima Lifshitz, and Kenneth M. Hoffman
From the Universitg of Maryland Hospital, Baltimore, Maryland, Rosewood State Hospital, Owings Mills, Maryland and the Department of Pediatrics, North Shore Hospital, Manhasset, New York, and the
Department of Pediatrics, Cornell University Medical College, New York, New York
ABSTRACT. A newborn infant with transient
mono-saccharide intolerance of noninfectious origin is
described. During the first day of life the patient
suffered severe anoxia with several episodes of
pro-longed apnea and cyanosis. On the second day of
life she was fed 5% glucose and water and severe
diarrhea ensued. After oral feedings were stopped
the diarrhea ceased. On the third and fourth day
of life similar episodes of diarrhea induced by
glu-cose and water feedings occurred. The stools were
acid and contained carbohydrates. However, when
the patient was fed sterile water or a carbohydrate
free diet, the diarrhea improved. The stools
re-mained normal with fecal pH of 7.0 and no
carbo-hydrates present as long as she was given no
carbo-hydrates by mouth during the first 22 days of life.
The intolerance to oral glucose extended to other
monosaccharides like fructose and D-xylose.
How-ever, after being free of diarrhea for 16 days she
began tolerating increasing quantities of glucose in
the diet. The capacity to tolerate fructose and
xy-lose was also recovered at 40 and 42 days of life.
Disaccharide intake was begun the 44th day of
life. She was fed dextrimaltose as a source of
car-bohydrate in the diet with good results. Sucrose
was not tolerated on the 67th day of life. Severe
diarrhea, dehydration, and metabolic acidosis
en-sued after “sugar and water” was fed. However,
this disaccharide was well tolerated by 150 days of
life. Lactose was not tolerated on the 81st day of
life. Milk formula feedings induced diarrhea with
stools being acid and containing large quantities of
carbohydrates. However, all dietary carbohydrates
were tolerated by 180 days of life, lactose was fed
with good results. The patient had no infection of
the upper segments of the small intestine
demon-strable to account for the monosaccharide and
di-saccharide malabsorption. It is tempting to
specu-late that anoxia in the newborn period might have
played a role in the intolerance to carbohydrates
seen in this patient during the first six months of
life. Pediatrics, 51 :891, 1973, ACQUIRED
MONOSAC-CHARIDE INTOLERANCE, DISACCHARIDE
INTOLER-ANCE, DIARRHEA, ANOXIA, HYPOXIA, NEWBORN.
- ,fONOSACCHABIDE malabsorplion may
.jv1
occur in infants1 and in adults.15’28Two
types
of monosaccharide
malabsorp-lion syndromes have been described: the primary, familial, autosomal recessive
in-herited disorder of specific
glucose-galac-tose malabsorplionhl28 and the secondary acquired, temporary nonspecific,
monosac-charide
malabsorplion
usually
associated
with infection of the upper segment of the small intestine.2227 In these latter groups of patients, there is an intolerance to all carbo-hydrates including monosaccharides such as fructose.
In
1967 Zetterstr#{246}m and Waldenstr#{246}m16 reportedtwo
infants who developed nonin-fectious diarrhea early in the neonatalpe-nod. They had a transient generalized
monosaccharide
malabsorption,
considered
to be a new familial syndrome. We describe a full-term infant who developed diarrhea immediately after she was fed glucose and
water
during
the
second
day
of
life.
She
had
monosaccharide
malabsorplion
during
the
neonatal
period
with
a
gradual
and
complete recovery of the capacity to toler-ate all carbohydrates in the ensuing six months. This patient, as well as those de-scribed by Zetterstr#{246}m and Waldenstr#{228}m16
may have an acquired monosaccharide
in-tolerance
syndrome
of noninfectious
origin.
CASE REPORT
K.H., a Negro female, was born after 39 weeks
I40
110
30 60
MINUTES
AFTER ORAL LOAD892
____________
_________________ ?N 39 WKS. GEST.L[LI!wE
iiiii:
IO
c,, 6.
z
5-z
0
12 20 22 24 28 32 40 42 44 69 II 50 60
DAYS OF LIFE
FIG. 1. The clinical course of KH is depicted in relation to the dietary
intake, number and type of stools and body weight. The fecal pH was
de-termined by the strip method. X = watery diarrhea! stools, #{176}
=
stools wereacid pH 6.0 and with carbohydrate 0.25% and 1+ glucose, #{176}= two liquid
stools contained 1% reducing substances. NPO = nothing by mouth (
fast-ing )
,
G/W = 5% glucose water, W = water, CHO-free = carbohydrate-freeformula, 5/W = “sugar water,” C = glucose, F = fructose, S = sucrose,
DM = dextrirnaltose, Xy
=
D-xylose, and TT = tolerance test.U,
CD
CD E
90
Fic. 2. The response to glucose and fructose oral
loads in a newborn infant with transient
mono-saccharide intolerance. The elevation in blood
reducing sugars following a fructose and a
glu-cose tolerance test are shown. The dose was 40
mg/sqm body surface area as a 20% solution.
The fructose tolerance test (.-
.
) on the 12thday of life induced severe diarrhea. In contrast,
an oral load of glucose (x-x ) on the 28th
day of life and an oral load of fructose ( #{149}- - - - #{149})
on the 48th day of life did not induce any
a!-teration in the stool patterns. Blood sugar was
done from the venous blood samples by the method of Somogyi-Nelson.
Labor was induced with pitocin and delivery was
precipitous under nonsterile conditions in a
commu-nity hospital. Birth weight was 2,070 gm; length,
43.5 cm; head circumference, 29.0 cm. Apgar score
at one minute was 1 and at three minutes was 5.
She required oxygen that was given by bag under
positive pressure. When she failed to respond, she
was intubated and given assisted respiration. At this
time 3 mEq/kg sodium bicarbonate were given
in-travenouslv as a rapid infusion. Her pulse rate was
80 per minute and her body temperature was 33.5C.
At five minutes of life, her Apgar score was 2. The
endotracheal tube was connected to a Byrd
respira-tor, set at a pressure of 20 mm Hg, and a rate of
50 respirations per minute. The arterial pH was
7.04, PCO., 37 mm Hg; Po2, 50 mm Hg; HCO., 9.5
mEq/liter; base excess, 20 mEq/Iiter. She was
again given 2 mEq/kg HCO-3 intravenously. After
this, her pulse was 120 to 130 per minute, and
res-pirations became spontaneous. The respirator was
disconnected at 30 minutes of age. Shortly
thereaf-ter the arterial blood pH was 7.13; PCO, 54 mm
Hg; Po2, 53 mm Hg; HCO-, 17; base excess, 11
mEq/liter, after she was taken off the respirator.
She was then given another 3 mEq of sodium
bi-carbonate and 3 cc of 50% dextrose. Her body
temperature started rising and was 35.5C at four
hours of age. Chest x-ray was normal. Subsequent
arterial blood gases determinations at 14 hours of
life showed a pH of 7.32; PCO2, 25; Po2, 63 mm Hg;
HCO-3, 12.5 mEq/liter, base excess, 12.
During the first day of life she had several
epi-sodes of prolonged apnea, cyanosis, jitteriness, and
893
TABLE I
PERTINENT LABORATORY DATA
Days of Life Laboratory Investigation Result
1 Gastric culture Sterile, no polymorphonuclear luekocytes on smear
Several Stool cultures No pathogens
13 Duodenal culture Sterile
14 Upper GI series Normal
15-18 Fecalfat (8.5 gm of fat intake per day) 0.2 gm of fat in stools per day
20 D-xylose tolerance test (300 mg/kg) Diarrhea induced, two of four liquid stools contained 1%
re-ducing substances. 5. 1% urine excretion in 5 hours
42 D.xylose tolerance test (300 mg/kg) Normal stools, 10.0% urine excretion in S hours
fluid and gastric fluid were cultured and
subse-quently revealed no growth. No pathogens were
grown from multiple stool cultures. However, she
was treated with penicillin and kanamycin (50,000
units/kg/day and 15 mg/kg/day; given
paren-terally for the next seven days of life. She was
given intravenously fluids containing at least 10%
glucose for the first 25 days of life. Some of the
pertinent clinical findings are shown in Figure 1,
and some of the pertinent laboratory data are
shown in Figure 2 and Table I.
On the second day of life, the apneic spells
dis-appeared. Thereafter, she had a regular breathing
pattern. Oral feedings were initiated with 15 ml of
5% glucose in water. She became tachypneic and
developed diarrhea immediately after being given
the first 15 ml of glucose and water. She had 13
watery stools during the next 12 hours. However,
after oral feedings were stopped, the diarrhea
ceased. On the third day of life, oral feedings were
again attempted. She ws given one feeding of 20
ml 5% glucose water and again developed
diar-rhea with severe abdominal distention. She had
seven liquid stools within the next eight hours. A
roentgenogram of the abdomen was negative. All
oral feedings were discontinued with prompt
im-provement. On the fourth day of life, she was
given one feeding of 30 ml of 5% glucose in water
which immediately induced diarrhea. She then had
six loose stools within the next 12 hours. At this
time, the feces were tested for pH and for the
presence of carbohydrates. The pH was acid (less
than 6.0) and the stool contained 1% reducing
substances. The patient developed metabolic
acido-sis, with a carbon dioxide of 12; sodium, 138;
potas-sium, 5.8; chlorine, 111 (mEq/liter). She was then
fed sterile water with prompt improvement of the
diarrhea. The serum carbon dioxide returned to 22
mEq/liter after 24 hours without alkali therapy.
On the sixth day, she was fed 30 ml of
full-strength carbohydrate-free diet#{176}every four hours
0 CHO-Free, Borden, Inc., New York, N.Y.
with continuation of the intravenous administration
of glucose solutions. The stools remained normal
with a fecal pH of 7.0 and no carbohydrates
pres-ent. Thereafter, the stools remained normal as long
as she was given no carbohydrates by mouth.
The intolerance to oral glucose extended to other
monosaccharides as well. When tested with an oral
load of fructose on the 12th day of life or D-xylose
on the 20th day of life, she immediately had
diar-rhea and excreted stools with an acid pH
contain-ing carbohydrates (Fig. 1). The serum reducing
sugars rose slightly after the fructose oral load with
a maximum increment of 19 mg/100 ml occurring
after 90 minutes ( Fig. 2 ) and the amount of
D-xylose recovered in the urine was only 5.1% of the
dose given (Table I).
On the 22nd day of life she was given 1% glucose
in the diet. This was well tolerated. The stools
re-mained normal with a neutral pH and with no
car-bohydrates. Two days later the amount of glucose in
the diet was increased to 2% with no change in
her stool pattern. On the 28th day of life, she
toler-ated an oral load of glucose (40 gm/sqm ) during
a glucose tolerance test without any diarrhea.
The serum reducing sugars showed a maximum
rise of 40 mg/100 ml at 45 minutes ( Fig. 2).
Therefore, glucose was added to the diet at a 5%
concentration and later at a 7% concentration. The
patient did not develop diarrhea. She began to gain
weight.
The capacity to tolerate other monosaccharides
was also recovered. At 40 days of age she was
given a repeat fructose oral load (40 gm/sqm)
which was tolerated. The stools increased in
num-ber, but remained of normal consistency, with a
pH of 7.0 and with no carbohydrates. The serum
reducing sugars attained a maximum increment of
34 mg/100 over fasting values after 45 minutes
(Fig. 2). At 42 days of life, she tolerated D-xylose
(300 mg/kg), 10% of the dose given was
ex-creted in the urine and she had two normal stools
in the following 24 hours.
894
MONOSACCHARIDE
INTOLERANCE
of life. The patient tolerated 8% dextrimaltose
added to the diet. The stools remained normal and
she continued gaining weight. The patient was
then discharged home. However, n the advice of
the local pharmacist, she was fed “sugar and
wa-ter” (sucrose ) because of “constipation” on the
67th day of life. Immediately, severe diarrhea
en-sued and she had to be readmitted to the hospital
with 10% dehydration and metabolic acidosis. On
admission the stools had an acid pH ( <6.0) and
contained 1% to 2% reducing substances. The
pa-tient was treated with intravenous fluids and
elec-trolytes and the diarrhea improved when fed an
electrolyte mixture containing glucose (Pedialyte)
or carbohydrate-free formula containing glucose,
but no disaccharides. After three days of no
diar-rhea, she was given a carbohydrate-free formula
containing 8% dextrimaltose with good results. At
81 days of age she was fed 500 ml of milk formula
in four divided feedings. Diarrhea developed and
she excreted five liquid stoools with an acid pH
and with 1% to 2% reducing substances.
Improve-ment followed immediately after milk was
discon-tinued. Patient was sent home.
When seen in the clinic two weeks after
dis-charge from the hospital, she had gained 540 gm
to 3.69 kg. Her length and head circumference
were 53.5 cm and 37.5 cm, respectively. Rice cereal
and fruits were added to the diet at 120 days of
age. One month afterwards, her weight had
in-creased to 5.0 kg. Sucrose was given as a source of
carbohydrate and was well tolerated. The patient
was begun on Isomil. She did very well and gained
425 gm more of weight in the next month. At 6
months of age the patient was started on milk
for-mula with no diarrhea. At present she is 8 months
old, she is fed a regular diet and has normal stools.
Her weight is 6.25 kg, length 65.0 cm, she sits up
and transfers objects from hand to hand and she is
neurologically normal for her age.
DISCUSSION
The
patient
reported
here
had
monosac-charide intolerance immediately after birth which persisted during the first month of life. This intolerance involved all monosac-charides tested such as fructose and D-xy-lose. During the acute phase of the illness,
she had diarrhea with acid stools contain-ing carbohydrates as long as the diet con-tamed sugar of any sort. The diarrhea im-proved promptly if all carbohydrates were
eliminated from the diet. However, the
ca-pacity to tolerate dietary carbohydrates gradually recovered during the ensuing six
months.
Zetterstr#{246}m and Waldenstr#{246}m’#{176}described two patients similar to the one reported here. They considered them to have a fa-milial generalized monosaccharide
malab-sorption
syndrome.
However,
all
previous
patients with the familial monosaccharide malabsorption syndrome have had a specific
malabsorption of only the actively trans-ported carbohydrates, glucose and galac-tose, and fructose was absorbed normally.
This alteration is inherited as an autosomal
recessive trait.121’29 These patients may have an abnormality of the glucose and ga-lactose binding sites of the intestine and kidney tubules which results in a selectively impaired glucose and galactose uptake.2#{176}
The
kinetic
analysis
of
the
absorption
of
glucose has indicated a reduced transport
capacity
(
Vmax)
and normal affinity for this carbohydrate(
Km). The heterozygotesfor this disorder have been detected by a similar specific reduced capacity for
glu-cose transport.29
The patients with acquired
monosac-charide
malabsorption
syndrome
have
a
generalized
malabsorption
of
all
carbohy-drates including fructose. This defect is temporary and limited to the intestine.
Ac-quired monosaccharide intolerance has been described in patients following sur-gery of the intestinal tract22 and diarrheal diseases of infancy.2327 These patients usu-ally have severe infection of the upper seg-ment of the small intestine.2227 The bacte-na! overgrowth of the small intestine might be the result of the cycle of events that may take place in infants with diarrhea.3#{176} This
cycle involves infection, carbohydrate
mal-absorption, and further proliferation of the bacteria into the upper segments of the
bowel.3#{176}Indeed,
monosaccharide
intoler-ance is usually found in patients with se-vere diarrheal disease who have had lactose intolerance for more than three weeks and!
or pneumatosis intestinalis2527,31
The patient reported as well as those of Zetterstr#{246}m and Waldenstr#{246}m16 had no
ARTICLES
895
patient had sterile gastric and duodenal
flu-ids. These patients may represent acquired
monosaccharide malabsorption of nonin-fectious origin. Secondary monosaccharide intolerance of any sort is usually associated with malabsorption of disaccharides as seen
in our patient.2527 On the other hand pa-lients with disaccharide malabsorption may or may not have monosaccharide
intoler-ance.31
It is tempting to speculate that anoxia
might have played a role in the intolerance to carbohydrates seen in this patient since
she had severe anoxia during the first 24
hours of life. Anoxia has been reported to alter intestinal functions. In rats and in fish, there is marked reduction in the absorptive capacity of the small intestine with glucose malabsorption occurring under hypoxia.3234 In other experimental animals, this condi-lion might destroy the enteric nerve
plex-uses, ganglion, and may induce histological damage.3541. Moreover, when hypoxia is ac-companied by epinephrine administration
there
may
be
gastrointestinal
ulcerations
induced.42
In seals during prolonged submergence43 and in fetuses and newborn infants sub-jected to stress, shock or hypoxia,44 there is reflex redistribution of circulation. Blood
may be shunted away from organs less vu1-nerable to anoxia such as kidneys and intes-tine, to the heart and brain. The local effect of this mechanism may be responsible for
production of ischemic necrosis of the bowel carbohydrate malabsorption,3234
and
monosaccharide
intolerance
as seen
in
our patient.
However,
anoxia
and
hypoxia
are
rela-lively frequent conditions occurring in
new-born infants. Hitherto, no occurrence of glucose intolerance has been associated with anoxia to our knowledge. On the other hand, such hypoxic patients may have pneumatosis intestinalis,1552 a condition
which may result from carbohydrate malab-sorption.25’53 Further investigations will be necessary to evaluate the role of anoxia and hypoxia in relation to carbohydrate
intoler-ance in the neonate.
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