Medicinal products and Glucose-6-PhosphateDéshydrogénase
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Documents
2008
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English
Ebook
2008
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Publié par
Publié le
25 février 2008
Nombre de lectures
51
Langue
English
25/02/2008
Publié par
Publié le
25 février 2008
Nombre de lectures
51
Licence :
Langue
English
Agence française de sécurité sanitaire
des produits de santé
143-147 boulevard Anatole France
F - 93285 Saint-Denis Cedex
www.afssaps.sante.fr
Indexby drugsubstances
Medicinal products
and-P-6sphotehaGuloces
Déshydrogénase)(DP6GDeficiency
february2008
Medicinal products and Glucose-6-Phosphate Dehydrogenase (G6PD)
deficiency
Only medicinal products evaluated before February 2008 are included in this document.
KEY MESSAGES
G6PD deficiency is a genetic disease that affects red blood cells.
It is due to the deficiency in one enzyme, Glucose-6-Phosphate Dehydrogenase, which is essential for the survival of red
blood cells.
Subjects deficient in G6PD can develop an acute haemolysis in case of oxidative stress. Some oxidative food or
medicinal products can provoke this haemolysis and therefore should be avoided whenever possible.
This booklet provides information on this disease, a pathways of the various cell oxidoreduction factors
list of medicinal products likely to provoke are insufficient to support life.
haemolysis (destruction of red blood cells) in G6PD
deficient subjects as well as what to do if you need The main clinical manifestation of G6PD deficiency
to prescribe or use these medicinal products. isaemolysish which could be observed according
to three clinical pictures:
G6PD DEFICIENCY haemolytic anaemia, induced by the- acute
ingestion of certain medicinal products or food, or
G6PD deficiency, also called favism, is themostduring an infection,
common enzymatic red blood cell hereditary- chronic haemolytic anaemia,
deficiency. It affects approximately420 million neonatal jaundice, with neurological- and
persons throughout the worldin the most severe and untreated cases. sequels, with a higher
frequency in Mediterranean basin, tropical African, Most of the time, apart from chronic haemolytic
Middle Eastern and tropical and sub-tropical Asian anaemia forms which are rare, the patient with the
countries African and Hispanic origin populations in deficiency does not show any special symptom.
North and South America and the Antilles are also
affected. A considerable clinical heterogeneity has been
observed depending on the molecular nature of the
According to the WHO data from 1989, the disease deficiency (variant) and the residual activity of the
prevalence is of 0.39% in Europe, which represents enzyme in the red blood cell. The WHO
in France 120,000 deficient male patients and classification of G6PD deficiency is based on the
approximately 1,400 new cases among male level of erythrocytic activity of the enzyme and
newborn babies. However, according to the latest extent of the clinical manifestations: class I: severe
*
estimates of the association Vigifavisme and its deficiency (1 to 2% of residual enzymatic activity);
Scientific Council, the number of subjects with a class II: intermediate deficiency (3 to 10% of
deficiency in France would be much higher, taking residual enzymatic activity);
into account the South North migrations from “High class III: moderate deficiency (10 to 40% of residual
risk regions of the World to France, and would enzymatic activity);
reach in 2007, more than 250,000 persons in
mainland France and overseas territories.ROLE OF GLUCOSE-6-PHOSPHATE
EDYHRDGONESA E
The disease is genetically transmitted on a
recessive X-linked mode. It mainly affects men, Glucose-6-Phosphate Dehydrogenase is a
called hemizygotes, while most of the time women cytoplasmic enzyme present in all cells. It catalyses
are only carriers of the anomaly. However there are the first reaction of thepentose phosphate
rare cases of women, called homozygotes, in whichpathway (transformation of sugars in energy
the deficiency is expressed. In heterozygote required for life).
women, the situation is complex due to the random
inactivation of one of the X chromosomes; they It produces:
have two red blood cell populations present in • ribose 5 phosphate (which will be used later
variable proportions from one individual to another. in nucleotide synthesis);
A total absence of activity has never been described • NADPH, coenzyme and main hydrogen
in humans because the other regeneration donor in numerous biosynthesis reactions. NADPH
is also essential for the destruction of hydrogen
peroxide (H2O2), highly toxic substance for the cell.
When the G6PD is not very active, NADPH
*Vigifavisme Association: French association of personsproduction via the pentose phosphate pathway
suffering from G6PD genetic
deficiency/www.vigifavisme.com
1
stops, which prevents glutathione reduction and
therefore the destruction of hydrogen peroxide.
G6PD plays an essential role in the reduction of
oxidative agents since without NADPH, hydrogen
peroxide will not be reduced and the cell will be
lysed (breaking of the cell due to the rupture of the
membrane).
Case of red blood cells:
The G6PD is normally present in all tissues,
however its deficiency is mainly expressed in red
blood cells within whichno other enzyme allows
NADPH production, unlike other nucleated cells in
the body.
In the absence of NADPH; any oxidative attack
results in an alteration of the main components of
the red blood cells (membrane and haemoglobin).
The denatured haemoglobin precipitates within the
cell to form inclusions called Heinz bodies, which
themselves generate toxic oxygen free radicals.
This denaturation of haemoglobin and the oxidation
of the membrane constituents lead to haemolysis
(destruction of red blood cells).
Following the haemolysis the red blood cells are
degraded in the liver which transforms the
haemoglobin in bilirubin. The bilirubin can then form
gallstoneswhich obstruct the gallbladder and could
cause jaundice. In certain cases, haemoglobin can
also be eliminated in urine and provoke and
haemoglobinuria.
When this haemolysis is large, it causesanaemia,
which results in organ failure.
SYMPTOMS LEADING TO SUSPECT
DEFICIENCY
Few hours or even some days after taking a trigger
agent, a sudden haemolysis attack can occur with:
• fever, pallor, headaches
• abdominal and lumbar pain
• excretion of dark urine
• unexplained fatigue or anorexia
• jaundice.
In neonates, the deficiency can be revealed by a
ndice) which starts towards
tjahue n2dnid(ce3ned an rodn .eaflialt aufo jysda
In case of hepatic colic or reoccurence of jaundice,
a lithiasis should be searched by ultrasonography.
TREATMENT
As a general rule, the treatment is mainly
preventive some food (refer to the excluding
“dietary advice" section) and avoiding some
medicinal products, whenever possible.
In case of a severe form, a blood transfusion, or
even an exchange transfusion, may be required.
It should be noted thatblood donation by a
subject with the deficiency is forbidden, and the
auto-transfusion is Not recommended.
TRIGGERING FACTORS
The trigger factor of a haemolysis could be the
ingestion of broad beans (fava in Italian), the
vegetable that gave the disease the name of favism.
In this case, the haemolysis and anaemia can occur
some hours after ingestion. They can be very
severe, with an acute renal failure associated and
require emergency treatment by transfusion or
exchange transfusion. They occur at any age.
Somemedicinal products can also cause
haemolysis in subjects with G6PD deficiency. The
influence of these products varies depending on the
individual and the type of deficiency. Individual
tolerance is unpredictable; therefore subjects
with a deficiency must follow the
recommendations related to medicinal products
and foodstuffs at risk.
DIETARY ADVICE
Subjects with G6PD deficiency can develop an
acute haemolysis following the ingestion of food.
The French healthcare product safety agency
(Afssa) has drawn up recommendations concerning
the diet of persons who suffer from G6PD deficiency
recommending
• not to consume fava beans (broad beans),
irrespective of their method of preparation and
consumption
• not to consume quinine-containing drinks
• be careful in case of major consumption of
products naturally rich in Vitamin C or foodstuff
enriched in vitamin C (like some fruit juices); the
Afssa also recommends not to consume vitamin-C
based dietary supplements.
These recommendations are available on the
internet site of the Afssa at the following address:
http://
www.afssa.fr/Documents/NUT2006sa0033.pdf.
In the case of chronic haemolysis
Folic acid (vitamin B9) supplementationmust not
be systematic even if the risk of deficiency is greater
in subjects with a deficiency than in the general
population. A supplement of 5 to 10 mg/day is
recommended in a systematic and intermittent
manner (1 to 2 weeks per months) in the following
cases: chronic haemolysis, scheduled pregnancy or
in progress, and following an infec
