INTRODUCTION:

Glucose-6-phosphate dehydrogenase deficiency, or G6PD deficiency for short, is the most common inborn metabolic disorder in the world. This means that from the time a baby is born, there is already something wrong with how his body makes and breaks important substances. According to statistics, about 400 million people have G6PD deficiency, and it is most common in Africa, Southeast Asia and the Middle East. Babies with G6PD deficiency have very little or no enzyme called Glucose-6-Phosphate Dehydrogenase (G6PD). An enzyme is a kind of protein that speeds up chemical reactions in the body. The enzyme G6PD is especially important to red blood cells. If this enzyme is lacking or missing, red blood cells are easily destroyed. Another name for G6PD deficiency is favism because some people who have it, usually those living in the Meditteranean region, react very badly to fava beans. Genes are like the bodys blueprints. They contain instructions on how specific parts of the body are made. For example, if the instructions in your hair genes say your hair is black, your hair will be black. Genes are packaged into threadlike structures called chromosomes. A chromosome is very much like a beaded bracelet. The beads are the different genes that give instructions for different part of the body; the entire bracelet is the chromosome. Genes usually come and act in pairs. One member of a specific pair comes from the father, and the other member comes from the mother. The members of a pair are located on paired chromosomes. All normal human beings have 23 pairs of chromosomes. Each of the first 22 pairs contain the same number and kind of genes. The last and 23rd pair is the sex chromosomes. They are different from the first 22 pairs in that they do not have the same number and kind of genes. The sex chromosomes contain the genes that determine whether a baby will be a girl or a boy. There are 2 kinds of sex chromosomes, X and Y. All baby girls have two X chromosomes. All baby boys have one X and one Y. The gene that gives instructions on how G6PD is made is found in the X chromosome only, thus G6PD deficiency is described as X-linked. If a baby girl gets one defective G6PD gene from either of her parents, she will not have G6PD deficiency because she has another G6PD gene that can do the work (remember: a baby girl has two X chromosomes, thus two G6PD genes). But if she gets two defective G6PD genes from both her parents, she will have G6PD deficiency. On the other hand, a baby boy whose G6PD gene is defective will surely get G6PD deficiency because the Y chromosome has no G6PD gene.A defective G6PD gene will give wrong instructions on how to make the enzyme G6PD. As a result, too little or none of it is made. G6PD deficiency is most common in African-American males. Many African-American females are carriers of G6PD deficiency, meaning they can pass the gene for the deficiency to their children but do not have symptoms; only a few are actually affected by G6PD deficiency. People of Mediterranean heritage, including Italians, Greeks, Arabs, and Sephardic Jews, also are commonly affected. The severity of G6PD deficiency varies among these groups it tends to be milder in African-Americans and more severe in people of Mediterranean descent.

PHYSICAL ASSESSMENT/ MANIFESTATIONS: Kids with G6PD deficiency typically do not show any symptoms of the disorder until their red blood cells are exposed to certain triggers, which can be:

illness, such as bacterial and viral infections certain painkillers and fever-reducing drugs certain antibiotics (especially those that have "sulf" in their names) certain antimalarial drugs (especially those that have "quine" in their names)

Some kids with G6PD deficiency can tolerate the medications in small amounts; others cannot take them at all. Check with your doctor for more specific instructions, as well as a complete list of medications that could pose a problem for a child with G6PD deficiency. Other substances can be harmful to kids with this condition when consumed or even touched such as fava beans and naphthalene (a chemical found in mothballs and moth crystals). Mothballs can be particularly harmful if a child accidentally swallows one, so ANY contact should be avoided. A child with G6PD deficiency who is exposed to a medication or infection that triggers the destruction of RBCs may have no symptoms at all. In more serious cases, a child may exhibit symptoms of anemia (also known as a hemolytic crisis), including:

paleness (in darker-skinned children paleness is sometimes best seen in the mouth, especially on the lips or tongue) extreme tiredness rapid heartbeat rapid breathing or shortness of breath jaundice, or yellowing of the skin and eyes, particularly in newborns an enlarged spleen dark, tea-colored urine

Once the trigger is removed or resolved, the symptoms of G6PD deficiency usually disappear fairly quickly, typically within a few weeks. If symptoms are mild, no medical treatment is usually needed. As the body naturally makes new red blood cells, the anemia will improve. If symptoms are more severe, a child may need to be hospitalized for supportive medical care

DIAGNOSTIC TEST: Glucose-6-phosphate dehydrogenase (G6PD) enzyme testing is used to screen for and help diagnose G6PD deficiencies. It may be used to screen children who experienced persistent jaundice as a newborn that could not be explained by another cause. Currently, newborns are not routinely screened for G6PD deficiency, but it is one of the thirty disorders that are recommended for screening by several organizations, including the March of Dimes. Result shows: Testing may also be done when other laboratory test results are consistent with a hemolytic anemia. These may show increased bilirubin concentrations (bulirubinemia), hemoglobin in the urine (hemoglobinuria), a decreased RBC count, an increased reticulocyte count, presence of "bite cells" on a blood smear, and sometimes the presence of Heinz bodies inside the RBCs on a specially stained blood smear. Result meaning: A low level of G6PD enzyme indicates a deficiency. An affected person is more likely to experience symptoms when exposed to a trigger. The results, however, cannot be used to predict how an affected person will react in a given set of circumstances. The severity of symptoms will vary from person to person and from episode to episode. A normal G6PD enzyme level in a male indicates that it is unlikely he has a deficiency, and if anemia is present, it is likely due to another cause. However, if the test was performed during an episode of hemolytic anemia, it should be repeated a few weeks later when the RBC population has had time to replenish and mature. Women who are carriers, having one altered and one normal gene copy (heterozygous), will have both G6PD-deficient and non-deficient RBCs. These women will usually have normal or near normal G6PD levels and rarely experience symptoms. A carrier will have a normal or low normal G6PD level, thus may not be identified through G6PD screening; however, the rare female who has two altered gene copies (homozygous) will show a significant decrease in G6PD level. Reference values are dependent on many factors, including patient age, gender, sample population, and test method, and numeric test results can have different meanings in different labs.

ANATOMY AND PHYSIOLOGY: Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) is a cytosolic enzyme in the pentose phosphate pathway (see image), a metabolic pathway that supplies reducing energy to cells (such as erythrocytes) by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH in turn maintains the level of glutathione in these cells that helps protect the red blood cells against oxidative damage. Of greater quantitative importance is the production of NADPH for tissues actively engaged in biosynthesis of fatty acids and/or isoprenoids, such as the liver, mammary glands, adipose tissue, and the adrenal gland. PATHOPHYSIOLOGY:

Predisposing Factor: GENETIC

Precipitating Factor: Maternal Status

G6P oxidation to 6phospogluconate Impaired RBC protection against oxidative damage Inability of RBC in increasing generation of NADPH Failure to withstand oxidative stress Damaged sulphydril groups of haemoglobin and RBC membrane

Haemolysis

RBC without nucleus and mitochondria Cannot carry protein synthesis

Jaundice

Enlarged spleen

Tea-colored urine

Metabolise glucose for ATP production

Extreme tiredness

Tachypnea

Tachycardia

G6PD DEFICIENCY