Glucose-6-Phosphate Dehydrogenase Deficiency

Glucose-6-Phosphate Dehydrogenase Deficiency

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Glucose-6-Phosphate Dehydrogenase Deficiency is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • G6PD Deficiency

Disorder Subdivisions

  • None

General Discussion

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PDD) is an inherited, sex-linked, metabolic disorder characterized by an enzyme defect that leads to the breakdown of red blood cells (hemolysis) upon exposure to stresses associated with some bacterial infections or certain drugs. A deficiency of this enzyme may result in the premature destruction of red blood cells (an acute hemolytic anemia or a chronic spherocytic type) when an affected individual is exposed to certain medications or chemicals, experiences certain viral or bacterial infections, and/or inhales the pollen of, or consumes, fava beans (favism).



Glucose- 6-Phosphate Dehydrogenase Deficiency is inherited as an X-linked genetic trait. It is a common inborn error of metabolism among humans. More than 300 variants of the disorder have been identified, resulting from mutations of the Glucose-6-Phosphate Dehydrogenase gene. The severity of symptoms associated with G6PD Deficiency may vary greatly among affected individuals, depending upon the specific form of the disorder that is present.



Neonatal G6PDD is particularly dangerous to an infant. It is manageable if caught early, and screening for the disorder is common.



The role of the enzyme G6PD is to maintain the pathway to generate a chemical called glutathione, which in a particular form is an antioxidant. The antioxidant is necessary to protect the cell's hemoglobin and its cell wall (red cell membrane). If the level of antioxidant is too low, then the cell's hemoglobin will not bind oxygen (its main purpose); the cell wall will break allowing the cell contents, including the modified hemoglobin, to spill out.

Symptoms

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.

Causes

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.)

Affected Populations

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.

Standard Therapies

Diagnosis

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.



Treatment

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.

Investigational Therapies

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

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



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 clinical2@na.amedd.army.mil.

References

TEXTBOOKS

Bennett JC, Plum F. Eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:856-58.



Berkow R, Beers M. Eds. The Merck Manual. 17th ed. Merck Research Laboratories, Whitehorse Station, NJ; 1999:2387-89.



Berkow R. The Merck Manual - Home Edition. Merck Research Laboratories, Whitehorse Station, NJ; 1997:749.



Larson DE, ed. Mayo Clinic Family Health Book. New York, NY: William Morrow and Company, Inc; 1996:962.



REVIEW ARTICLES

Kaplan M, Hammerman C. Glucose-6-phosphate dehydrogenase deficiency: a potential source of severe neonatal hyperbilirubinaemia and kernicterus. Semin Neonatol. 2002;7:121-8.



Hundsdoerfer P, Vetter B, Kulozik AE. Chronic haemolytic anaemia and glucose-6 phosphate dehydrogenase deficiency. Case report and review of the literature. Acta Haematol. 2002;108:102-5.



Southgate WM, Wagner CL, Wagstaff P, Purohit DM. Hyperbilirubinemia in the newborn infant born at term. J S C Med Assoc. 2002;98:92-8.



Bates N. Mothball poisoning. Emerg Nurse. 2002;10:24-8.



Gaskin RS, Estwick D, Peddi R. G6PD deficiency: its role in the high prevalence of hypertension and diabetes mellitus. Ethn Dis. 2001;11:749-54.



Clague A, Thomas A. Neonatal biochemical screening for disease. Clin Chim Acta. 2002;315:99-110.



FROM THE INTERNET

Fisher T. Glucose-6-phosphate dehydrogenase deficiency. Discovery Health. Encyclopedia of Diseases and Conditions. 2002:3pp.

http://health.discovery.com/diseasesandcond/encyclopedia/113.html



MEDLINEPlus. Medical Encyclopedia. Glucose-6-phosphate dehydrogenase deficiency. 2002:4pp.

www.nlm.nih.gov/medlineplus/encyclopedia.html



Italian Favism Association. G6PD Deficiency Guide. 2002:4pp.

www.favism.org



Carter SM, Gross SJ. Glucose-Phosphate Dehydrogenase Deficiency. emedicine Journal. 2002:6pp.

http://www.emedicine.com/med/topic900.htm



McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 305900: Last Up-Date; 10/22/02.



McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 134700: Last Up-Date; 2/17/99.

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



Parents of Infants and Children with Kernicterus (P.I.C.K.)

One W. Superior Street

Suite 2410

Chicago, IL 60610

USA

Tel: (312)274-9695

Email: info@pickonline.org

Internet: http://www.pickonline.org/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



G6PD Deficiency Association [Associazione Italiana Favismo, onlus]

Via Amba Aradam 12

30173 Mestre-Venice

Italy

Tel: 0416391105

Fax: 0415347807

Email: info@favismo.it

Internet: http://www.g6pd.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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