Monday 11 April 2011

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY



What is G6PD deficiency

  • G6PD deficiency is a genetic disorder
  • G6PD deficiency caused due to a deficiency of a chemical enzyme called glucose-6-phosphate dehydrogenase found in the RBC (red blood cells) causes red blood cells to break down prematurely.
  • This syndrome is more common in males than females. Usually female became carrier.
  • This deficiency did not show any symptom but after exposure to certain medicines, foods, and other infections, it causes severe injury to red blood cells by breaking the RBC's down
  • Destruction of red blood cells is called hemolysis. If not properly treated, it will cause kernicterus.
  • Once you get this disease, it can be either life long process or it could be cured.
  • Typically,  easily curable with proper medicine

Symptoms of G6PD deficiency
  • typically do not show any symptoms of the disorder until their red blood cells are exposed to certain triggers, which can be:
       Øillness, such as bacterial and viral infections
Øcertain painkillers and fever-reducing drugs
Øcertain antibiotics (especially those that have "sulf" in their names)
Øcertain antimalarial drugs (especially those that have "quine" in their names)
  • In more serious cases
    Øpaleness (in darker-skinned children paleness is sometimes best seen in the mouth, especially on the lips or tongue)
    Øextreme tiredness
    ØRapid heartbeat
    ØRapid breathing and shortness of breath
    Øjaundice, or yellowing of the skin and eyes, particularly in newborns
    ØAn enlarged spleen
    Ødark, tea-colored urine


  • Jaundice is one of the big side effects of G6PD deficiency. Newborn babies can have this disorder
ØThe main symptom of jaundice is a yellowish color of the eyes and mucous membrane.
ØG6PD causes jaundice by breaking down the red blood cells
Ø With jaundice, the baby's liver can not properly filter out toxins from the child's system, then lead to even more serious health problems
  • For adult – if you get G6PD deficiency:
Ø You should avoiding eating beans – this food  increases the breakdown of red blood cells in this condition
Ø You should never use mothballs in your clothing or closets – these can exacerbate the disease
ØYou need proper medical treatment to make sure you have no lasting negative health effects 

Common affected of G6PD
  • Distribution – most frequently in certain parts of Africa, Asia, and the Mediterranean
  • An estimated 400 million people worldwide have glucose-6-phosphate dehydrogenase deficiency
  • It affects about 1 in 10 African-American males in the United States

The gene related to G6PD
  • G6PD is genetic disorder that related to mutations in the G6PD gene
  • The G6PD gene provides instructions for making an enzyme called glucose-6-phosphate dehydrogenase.
  • This enzyme functions as:
       Ø normal processing of carbohydrates
Øprotects red blood cells from the effects of potentially harmful molecules called reactive oxygen species - Reactive oxygen species are byproducts of normal cellular functions that building up to toxic levels within red blood cells
  • If the G6PD deficiency by mutation, reactive oxygen species can accumulate and damage red blood cells
  • Then, factor such as infections, certain drugs, or ingesting fava beans can increase the levels of reactive oxygen species causing red blood cells to be destroyed faster than the body can replace them. Afterward, it will cause hemolytic anemia
  • carriers of a G6PD mutation may be partially protected against malaria, an infectious disease carried by a certain type of mosquito. Glucose-6-phosphate dehydrogenase deficiency occurs most frequently in areas of the world where malaria is common

How people inherit G6PD deficiency 
  • This condition is inherited in an X-linked recessive pattern
  • The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes
  • In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition.
  • In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder.
  • Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females.
  • A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons

Diagnosis and treating G6PD deficiency
  • G6PD deficiency go undiagnosed until symptoms have been develop
  • To confirm the diagnosis usually use blood tests and to rule out other possible causes of the anemia
  • Treating the symptoms associated with G6PD deficiency is usually as simple such treating the illness or infection or stopping the use of a certain drug
  • But, severe anemia may require treatment in the hospital to receive oxygen, fluids, and, if needed, a transfusion of healthy blood cells
  • In rare cases, the deficiency can lead to other more serious health problems


Haemolytic disease of newborn (HDN)

Is an alloimmune condition that develops in a fetus
 when the IgG molecules produced by the mother pass
 through the placenta
This fetal disease ranges from mild to very severe,
 and fetal death from heart failure (hydrops fetalis
can occur
Antibodies are produced when the body is exposed 
to foreign antigen 
Some of the develeped antibodies can attack the body sistem
 and causing the reticulocytosis and eventually lead to anemia
If present in the fetus, and may affect it in utero and 
persist after delivery 
Rh disease is the most common form of severe HDN 
and it varies from mild to severe

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HOW TO DIAGNOSE


The diagnosis of HDN is based on history and laboratory findings

Blood tests done on the newborn baby

I.Biochemistry tests for jaundice
II.Peripheral blood morphology shows increase
reticulocytes. Erythroblasts (also known as 
nucleated red blood cells) occur in moderate and 
severe disease.
III.Positive direct Coombs test (might be negative 
after fetal interuterine blood transfusion)

Blood tests done on the mother

                  Positive indirect Coombs tests

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Biochemistry Test for Jaundice

Jaundice is yellow discolouration of skin, sclera, mucous
membranes, and other tissues due to excess of bilirubin in the
blood.
Occurs when there is too much bilirubin circulating in the
blood.


*Bilirubin is a compound produced when hemoglobin is broken down in the blood.

1. Examination of feces 

The stools are dark colored in hemolytic jaundice due to
excessive bile pigment, whereas it is pale and chalky white (clay
coloured) in obstructive jaundice due to absence of bile. 


2. Serum bilirubin

The total, conjugated and unconjugated fractions can be
estimated. This helps in assessing the severity of jaundice 
and also in identifying the type. 

Vandenberg reaction 
is a qualitative test used in detecting the type of bile pigment in 
the serum.Direct positive test is given by conjugated bilirubin,
unconjugated bilirubin gives rise to the indirect reaction. When 
both pigments are present the reaction is biphasic.


Positive Direct Coomb Test

The direct Coombs' test is used to detect antibodies that are 
already bound to the surface of red blood cells.
These antibodies sometimes destroy red blood cells and cause
anemia.

Normal result:No clumping of cells (agglutination).
                         indicating that there are no antibodies to red         
                         blood cells.

* mother have anti-D antibodies baby blood will test for anemia and jaundice



This may occur when there is a baby-mother Rh
incompatibility.


The most common cause of hemolytic disease of the newborn is
an ABO incompatibility between mother and baby, especially 
with mothers that are blood group O.




Indirect Coomb's Test

The indirect Coombs test finds certain antibodies that are in the
liquid part of the blood (serum).


A test to determine whether a woman has Rh-positive or Rh
negative blood (Rh antibody titer) is done early in pregnancy. If
she is Rh-negative, steps can be taken to protect the baby.



Normal result
      
      A negative indirect Coombs test for Rh factor (Rh antibody titer) in a pregnant woman means that she has not developed antibodies against the Rh-positive blood of her baby.
     This means that Rh sensitization has not occurred.

Abnormal result
      
      If the Rh antibody titer test is positive in a woman who is pregnant or is planning to become pregnant, it means that she Rh sensitizationhas antibodies against Rh-positive blood