Originally posted by MooKu:
Dec 4, 2006
[b]Take heart - there is a reason and a gene test
By Senior Writer, Andy Ho
ONE day in April, former TV journalist Derek Cher was found slumped
at his desk in the office. He had died of unknown causes.
Then, in October, three others - teenager Danil Shagimardanov, 16;
Dr Christopher Lim Kim Tho, 35, a registrar in orthopaedic surgery
at the KK Women's & Children's Hospital; and store manager Soh
Chee Yong, 25 - were each separately and on different days found
dead in bed.
And just last month, Dr Toh Wei Keong, 32, a general practitioner,
also died in his sleep.
All were apparently healthy individuals, with no previous history
of heart problems or family history of sudden deaths.
But such devastating tragedies are not unique to Singapore. Similar
cases in young Thai men are called 'lai tai'. Likewise, they are
named 'bangungut' in the Philippines and 'pokkuri' in Japan.
Common to the folklore in these countries is unexplained sudden
death in apparently healthy young men in their sleep, sometimes
preceded by thrashing.
Excluding Danil, who was still just a boy and of Kazakh extraction,
the other victims fit the profile of sudden nocturnal deaths in
young South-east Asian males: Dr Lim's wife had observed him having
a 'seizure' before he died, although Dr Toh's wife had not noticed
anything amiss.
According to a recent Health Sciences Authority study, an average
of 300 men aged between 18 and 60 die suddenly in Singapore each
year. Most of these deaths are caused by heart conditions, though
people also die in their sleep from an asthmatic attack, a stroke,
the rupture of an enlarged blood vessel or sleep apnea, where one's
breathing stops due to an obstruction in the airways.
But no cause of death can be identified in 3 per cent of these
cases, while the percentage of those who die in their sleep is also
not known.
Readers have asked if there is a link among all these recent cases.
Though many local experts feel there is none, there is an
intriguing possibility, a condition that is rare in the West but
more common in young men in South-east Asia and Japan, as folklore
has it.
Doctors call it the Brugada
syndrome.
Back in the late 1980s and early 1990s, about 200 apparently
healthy Thai foreign workers in Singapore died from no apparent
cause. These were later identified as cases of Brugada syndrome, a
mysterious condition in which spontaneous abnormal heart rhythms
kill victims in their sleep.
In the early 1990s, when the syndrome was first identified, the
cause was still unknown. After all, the heart in such victims
looked normal under the microscope. At the time, experts postulated
various causes for death, such as heart rhythms going awry in some
unspecified way.
But most of their hypotheses turned out to be quite mistaken. With
the genomics revolution, the cause
has now been identified as mutations in seven particular genes,
which are specific segments of the DNA code we all
carry.
This cause has been confirmed by different groups of experts in
various countries, so Brugada syndrome is now regarded as
an inheritable heart
condition.
How does it kill? The short answer
is that these mutations affect what are called 'ion channels' that
are found in the living membrane that covers each heart muscle
cell. These channels are really protein complexes structured like
tubes running through the thickness of a cell membrane. What they
do is to permit - or restrict - the movement in and out of heart
cells of positively charged atoms, or ions, of potassium and
sodium.
This movement of ions in and out of cells generates a voltage
difference between the inside and outside of the cell.
That voltage difference, in turn, gives rise to electric signals in
the membrane that go around the heart, causing the organ to beat
rhythmically.
These electrical signals stimulate the heart chambers to contract
in the correct order - regularly and continuously - thus pumping
blood throughout the body.
Should this electric activity be disrupted, however, the heart may
fail to be effective as a pump. When this happens, the patient
could suffer a blackout.
Or he may notice palpitations.
Worse still, his heart could stop beating and pumping, so death
would occur suddenly.
In short, if you carry mutations that produce abnormal ion
channels, which regulate the flow of electrical charge, your
heart's electric activity could be disrupted without warning. This
is what happens in Brugada syndrome.
Since ion movements occur only in life, the heart will appear
structurally normal when death strikes in such cases.
To summarise a complex process, this is a case which sees abnormal
channels letting potassium ions in too slowly, or sodium ions too
quickly.
But there is a small difference: Potassium channel problems are
associated with sudden death that is usually brought on by exercise
or if the person is startled or awoken suddenly; sodium channel
problems are more likely to be associated with death while one is
asleep.
Still, the illness is rare indeed. Japanese studies suggest that
only 0.05 per cent to 0.6 per cent of adults have ECGs that are
compatible with a diagnosis of Brugada syndrome. Published studies
elsewhere show that Brugada syndrome is responsible for probably 4
per cent to 12 per cent of unexpected sudden deaths.
So should you be worried?
If you do not have an ECG that is compatible with Brugada syndrome,
a history of fainting spells or a family history of sudden
unexplained nocturnal deaths, you are probably not at risk.
But if you have a positive family history, you should avail
yourself of not just an ECG, but also some very sensitive DNA-based
tests that have just become available for routine clinical use. In
fact, all immediate blood relatives of someone who has had an
unexplained and unexpected sudden death should have such tests done
to find out if they have inherited similar mutations.
And that goes for women relatives too. While Brugada syndrome is
more common among males, females are not spared.
In 2004, Dr Hong Kui, in collaboration with Dr Ramon Brugada - both
based in New York - and the latter's brother, Dr Josep Brugada of
Spain's University of Barcelona, as well as other scientists,
noticed that, for affected women, the immediate period after giving
birth to a baby seems to be a particularly risky one.
Identifying those at risk can lead to preventive measures for some,
including taking drugs called beta blockers, which modulate the
heart rhythm.
Also pacemakers or cardiac defibrillators could be implanted. These
gadgets prevent dangerous heart rhythms from taking over, with the
latter also being capable of delivering an electric shock to reset
the ticker, when needed.
Testing to identify the vulnerable will undoubtedly save lives.
Five people have already perished, so hospitals in Singapore should
lose no time in adopting a policy of testing the immediate
relatives of such victims. One person lost to Brugada syndrome is
one too many.
[/b]
Mooku taking over Oxford Mushroom's Forum Physician
position?
