Transcript Glucose -6 phosphate dehydrogenase deficiency

Done by : Bara Shayib
Supervised by : Dr . Abdullateef
Alkhateeb
What is G6PD?
 Stands for Glucose 6 phosphate dehydrogenase
 x- linked disease – autosomal recessive
 Gene Map Locus: Xq28
 Most individuals with G6PD deficiency have a
qualitative abnormality in the structure of the G6PD
enzyme
Cont…
 glucose-6-Phosphate Dehydrogenase(G6PD)
deficiency is the most common human enzyme
deficiency; an estimated 400 million people worldwide
are affected by this enzymopathy
 a metabolic enzyme involved in the pentose phosphate
pathway, especially important in red blood cell
metabolism
Cont…
 Individuals with the disease may exhibit nonimmune
hemolytic anemia in response to a number of causes,
most commonly infection or exposure to certain
medications or chemicals
 G6PD deficiency is closely linked to favism, a disorder
characterized by a hemolytic reaction to consumption
of broad beans
Epidemiology
G6PDH is the most common
human enzyme defect, being
present in more than 400 million
people worldwide. African, Middle
Eastern and South Asian people are
affected the most
Function
Accumulation of oxidants
Hemolytic anemia
Neonate jaundice
Infections
Hemolysis
 Oxidation of the sulfhydryl groups on hemoglobin leads to
the formation of methemoglobin and then denatured
globin or sulfhemoglobin, which form insoluble masses
that attach to the red cell membrane (called Heinz bodies)
 The net effect is that the deficient red cells become rigid
and nondeformable, making them susceptible to
destruction by reticuloendothelial macrophages in the
marrow, spleen and liver Although this type of hemolysis is
predominantly extravascular, intravascular hemolysis also
occurs, leading to hemoglobinemia and hemoglobinuria
Jaundice
 The clinical picture of neonatal jaundice in this setting
differs from classic neonatal jaundice in two main
respects :
 First, G6PD deficiency related neonatal jaundice is
rarely present at birth; the peak incidence of clinical
onset is between days two and three
 Second, there is more jaundice than anemia, and the
anemia is rarely severe
Cont…
 The pathogenesis of this type of neonatal jaundice
remains uncertain. Some believe that decreased
hepatic bilirubin elimination is a key factor while
others maintain that increased hemolysis causes the
hyperbilirubinemia
 We afraid from kernicterus
Accumulation of glucose
Diabetes milletus
Decreased NADPH
Hypertension
Classification
 (Type 1 ) Severe deficiency (<10% activity) with chronic
(nonspherocytic) hemolytic anemia
 (Type 2) Severe deficiency (<10% activity), with intermittent
hemolysis
 (Type3) Mild deficiency (10-60% activity), hemolysis with
stressors only
 (Type 4) Non-deficient variant, no clinical sequelae
 (Type5) Increased enzyme activity, no clinical sequelae
Diagnosis
 The diagnosis is generally suspected when patients
from certain ethnic groups develop anemia, jaundice
and symptoms of hemolysis
 Positive family history
Cont…
 Complete blood count and reticulocyte count; in active
G6PD, Heinz bodies can be seen in red blood cells on a
blood film
 Liver enzymes (to exclude other causes of jaundice)
 Lactate dehydrogenase (elevated in hemolysis and a
marker of hemolytic severity)
 A "direct antiglobulin test" (Coombs' test) – this
should be negative, as hemolysis in G6PD is not
immune-mediated
Cont…
The Beutler fluorescent spot test
direct DNA testing and/or
sequencing of the G6PD gene
Treatment
 The most important measure is prevention--
-- avoidance of the drugs and foods that
cause hemolysis
 Vaccination against some common
pathogens
 n the acute phase of hemolysis, blood
transfusions might be necessary
Cont…
 dialysis in acute renal failure
 removal of the spleen (splenectomy)
 Although vitamin E and selenium have
antioxidant properties
G6PD in other hematopoietic cells
 Leukocyte and platelet G6PD is regulated by the same
gene as that in red cells; as a result, deficient
individuals have reduced enzyme activity in these
cells, particularly patients with more severe enzyme
deficiency such as G6PD Mediterranean
 However, this abnormality is rarely associated with
functional impairment of leukocytes and platelets due
to their normally short survival. As an example,
phagocytic and bactericidal activity of granulocytes are
typically normal in deficient subjects
Prognosis
 G6PD-deficient individuals do not appear to acquire
any illnesses more frequently than other people, and
may have less risk than other people for acquiring
(ischemic heart disease)and cerebrovascular disease
 Possible protection against malaria
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