Dr KK Aggarwal
What do we know so far about
these deaths: Mostly malnourished children < 10 years old, linked to
lychee orchids, convulsions early in the morning, no fever, high mortality the
same day, all had low sugar but mortality still high even after infusing sugar.
This only means that some
other metabolic factor is also at play apart from the sugar.
What might be happening? If
significantly malnourished children, who have not eaten food for more than 3
days eat oral carbohydrates (litchi in this case), it can cause electrolyte and
fluid shifts that may precipitate disabling or fatal medical complications.
This is the so-called
refeeding syndrome characterized by hypophosphatemia, hypokalemia, congestive
heart failure, peripheral edema, rhabdomyolysis, seizures, fever and
hemolysis. The hallmark feature is hypophosphatemia.
Rapidly treating hypoglycemia
with lychee will harm, if phosphate levels are not managed. The best food in
such situations is sugarcane juice and not litchi. Remember, sugarcane is the
juice used to break all starvation fasts.
The risk of hypophosphatemia
during refeeding appears to be greater in patients who are more severely
malnourished and at lower percent of ideal body weight.
Stores of phosphate are
depleted during episodes of starvation. When nutritional replenishment starts
and patients are fed carbohydrates, glucose causes release of
insulin, which triggers cellular uptake of phosphate (and potassium and
magnesium) and a decrease in serum phosphorous levels. Insulin also causes
cells to produce a variety of depleted molecules that require phosphate
(adenosine triphosphate and 2,3-diphosphoglycer1ate), which further depletes
the body’s stores of phosphate.
The subsequent lack of
phosphorylated intermediates causes tissue hypoxia, myocardial dysfunction,
respiratory failure due to an inability of the diaphragm to contract,
hemolysis, rhabdomyolysis and seizures.
Risk factors for the
re-feeding syndrome include low baseline levels of phosphate, potassium, or
magnesium prior to re-feeding the patient; and little or no nutritional intake
for the previous 5 to 10 days. Patients are at the highest risk for the
re-feeding syndrome in the first 1 to 2 weeks of nutritional replenishment and
weight gain.
Generally, the risk
progressively dissipates over the next few weeks if there has been consistent
forced intake and weight gain.
Excerpts from Dr T Jacob John,
Retired Professor of Virology from CMC Vellore
· All
it would have taken was to ensure that the children had a meal the preceding
night
· The
disease is not encephalitis but encephalopathy.
· Encephalitis
results from a viral infection, unless proved otherwise. The pathology is
primarily in the brain. Encephalopathy is a biochemical disease, unless proved
otherwise.
· Encephalopathy
is eminently treatable.
· Hypoglycemia
is usually due to an overdose of insulin in children with diabetes. It is
easily corrected with oral sugar or intravenous glucose. The easily available
5% glucose solution suffices. Hypoglycaemic encephalopathy, however, is
different from simple hypoglycemia.
· The
disease broke out during the months when litchi was harvested, i.e. April, May
and June. The illness started suddenly; children were found vomiting, displayed
abnormal movements, were semi-conscious, and were convulsing between 4 a.m. and
7 a.m. The disease progressed fast — children went into coma and died within a
few days. When sick children were tested, the blood glucose level was always
below normal.
· This
disease was reminiscent of the Jamaican Vomiting Disease, a form of
hypoglycaemic encephalopathy. It is triggered when unripe cake fruits are
eaten. These fruits contain a substance, ethylene cyclopropyl alanine, which
blocks a biochemical process called fatty acid oxidation, or gluconeogenesis.
· There
are two essential steps: gluconeogenesis is turned on and is then blocked
midway by methylene cyclopropyl alanine. The back-up molecules of the
unfinished process are certain amino acids that are highly toxic to the brain
cells. Ackee and litchi belong to one plant family. We found generous
quantities of methylene cyclopropyl glycine in litchi fruit pulp.
· The
disease affected only malnourished children between the ages of two and 10.
· A
majority of them were from families camping in orchards for fruit harvesting.
No child from the nearby towns fell ill. Children of well-to-do families never
fell ill.
· Litchi
harvest usually begins by 4 a.m., which means that families are awake before
that. They go to sleep early. If children go to sleep without dinner, parents
usually do not wake them up and feed them. Litchis are collected in bunches and
sent to the collection points, but single fruits fall to the ground. Children
are free to collect and share the fruits with their friends.
· After
prolonged fasting, malnourished children slipped into hypoglycaemia in the
morning. Since they had very little reserve glycogen in their livers, they were
unable to mobilise glucose from liver glycogen, unlike well nourished children.
The brain needs glucose as a source of energy. As a result of lack of liver
glycogen, gluconeogenesis was turned on. Had there not been litchi methylene
cyclopropyl glycine, the glucose levels would have been maintained, and the
children would have come to no harm. As the children had consumed litchis the
previous day, gluconeogenesis had been blocked, aminoacidemia had developed,
and brain functions had been affected. Hypoglycaemic encephalopathy had set in.
· We
were unable to demonstrate aminoacidemia in children with hypoglycaemic
encephalopathy, but that was done by investigators from the US Centers
for Disease Control and Prevention (CDC). The only missing piece in
our studies was filled in by CDC colleagues.
· The
disease can be prevented if children are well nourished, but that is not
possible in the immediate term. It can also be prevented by ensuring that
children eat a meal at night. All families were taught to provide a cooked meal
to children before going to sleep at night. Preventing children from eating
litchis is not easy, but the quantity of the fruit can be restricted with
parental supervision. With all this health education, I was told that the
disease number had come down drastically in 2016-18 compared to what it was in
2014-2015. I don’t know what went wrong this year.
· In
2015, all primary health centres were supplied with glucometers to check the
blood glucose levels of sick children. Doctors were instructed to take a blood
sample for glucose estimation and, irrespective of the results, infuse 10%
glucose intravenously. To correct mild hypoglycaemia, 5% glucose is enough, but
here the problem is not hypoglycaemia alone, but aminoacidemia as a
result of blocked gluconeogenesis. To prevent any further back-up
amino acid from accumulating, the fatty acid oxidation process has to be turned
off quickly. That requires raising blood glucose level to abnormally high
levels so that insulin secretion is stimulated, and that in turn turns off the
gluconeogenesis.
· If
ill children are infused with 10% glucose within four hours of onset of brain
dysfunction, recovery is fast and complete. If only 5% glucose
is given, or if 10% glucose is not administered within four hours, recovery is
unlikely.
· Glucometers
have not been maintained well. Health education was not sustained. New doctors
are not familiar with all the information. Instead of 10% glucose, 5% is given.
· Ambulances
take more than four hours to reach the city hospitals from many rural clinics.
The final answer
· Refeeding
syndrome
· Shortened
duration added with litchi toxins
· Prevention:
Evening mid-day meal
· In
hospital, treat low sugar, low phosphates, low magnesium, low potassium
Dr KK Aggarwal
Padma Shri
Awardee
President Elect Confederation of
Medical Associations in Asia and Oceania
(CMAAO)
Group
Editor-in-Chief IJCP Publications
President Heart
Care Foundation of India
Past National President
IMA
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