The severity of symptoms associated with (G6PDD) varies greatly from case to case, depending upon the form of the disorder that is present, and some people have no symptoms at all. When symptoms are present, they may include fatigue, pale color, shortness of breath, rapid heart beat, jaundice or yellow skin color, dark urine and enlarged spleen (splenomegaly).
In the relatively rare, severe, potentially life-threatening cases, symptoms include, in addition to those listed above, others such as: blood in the urine (hemoglobinuria), shock, kidney (renal) failure and congestive heart failure in which the heart is unable to pump blood effectively throughout the body.
Most affected individuals, when exposed to fava beans, will experience severe episodes of hemolytic anemia due to such exposure (Favism). Others, with still other variants of G6PD Deficiency, may present no symptoms whatsoever.
Chromosomes, which are present in the nucleus of human cells, carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males, and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13″ refers to band 13 on the short arm of chromosome 11.
Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
Glucose-6-Phosphate Dehydrogenase Deficiency is inherited as an X-linked trait. The responsible gene has been mapped to Xq28.
X-linked recessive disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons.
In X-linked dominant disorders, the female with only one X chromosome affected will develop the disease. However, the affected male always has a more severe condition. Sometimes, affected males die before birth so that only female patients survive.
In some affected individuals, episodes of Hemolytic Anemia due to G6PD Deficiency may result from exposure to certain drugs. Among the many that have been cited as causative agents are: Aspirin, Acetanilid, Methylene Blue, Nalidixic Acid, Naphthalene, Niridazole, Nitrofuratoin, Pam aquine, Pentaquine, Phenylhydrazine, Primaquine, Sulfacetamide, Thiazolesulfone, Toluidine Blue, and Trinitrotoluene. Such episodes may also result in some affected individuals due to diabetic acidosis, certain viral and bacterial infections, and/or exposure to fava beans (Favism) or certain derivatives of Vitamin K. (For more information on Favism, see the Related Disorders section of this report.)
As mentioned above, Glucose-6-Phosphate Dehydrogenase Deficiency is one of the most common forms of enzyme deficiency and is believed to affect approximately 400 million people worldwide. The highest prevalence rates are found in Africa, New Guinea, the Middle East, certain parts of the Mediterranean, and certain areas in Asia. In these regions, the rate ranges from 5% to 25% of the population.
Over 400 variants of the disorder have been identified, resulting from different mutations of the Glucose-6-Phosphate Dehydrogenase (G6PD) gene. In the United States, the incidence of G6PDD is much higher among the Afro-American population than in other sectors. The frequency of a carrier state in which one partner carries a normal gene and the other carries an abnormal variant is as high as 24%. About 10%-14% of Afro-American males are affected. For example, two common variants occur in many African-American males. Approximately 20 to 25 percent have the near normal G6PD variant called “A+”, while about 10 to 13 percent have another variant called “A-“. Another relatively common G6PD variant is found particularly among individuals of Sephardic Jewish or Sardinian descent. In addition, another somewhat common variant is present among some individuals of southern Chinese descent. In many cases, the disorder is not diagnosed because most individuals do not experience serious symptoms unless they are exposed to certain drugs (usually oxidants) or other specific stressors.
If jaundice and anemia occur together, a diagnosis of G6PDD is suspected. The diagnosis is confirmed by blood tests that determine the volume of red blood cells circulating. Further supporting evidence may be had by means of tests that measure the intensity of the enzyme activity itself.
Glucose-6-Phosphate Dehydrogenase Deficiency is best managed by preventative measures. Individuals should be screened for the G6PD defect before being treated with certain drugs such as antimalarials and other medications. (See above for a partial list of medications to be avoided. People with G6PD Deficiency should not eat fava beans, nor be exposed to areas where fava beans grow.
If an episode of Hemolytic Anemia is due to the use of certain medication, the causative drug should be discontinued under a physician’s supervision. If such an episode is due to an underlying infection, appropriate steps should be taken to treat the infection in question. Some cases may require the administration of oxygen to the patient. Other patients may need short-term treatment with fluids or even blood transfusions.
Neonatal jaundice is treated by placing the infant under special lights (bili lights) that alleviate the jaundice.
Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
The Walter Reed Army Institute of Research is sponsoring (2005) a study to evaluate a new testing method for identifying medicines that can cause problems in G6PD-deficient individuals. Volunteers with G6PD deficiency willing to donate blood samples are being sought. For information, call (866) 856-3259 or write to firstname.lastname@example.org.
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