Última actualización:
August 07, 2020
Años publicados: 1986, 1987, 1990, 1995, 1996, 2006, 2007, 2020
NORD gratefully acknowledges Elizabeth L. Kugelmann, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Summary
Hereditary nonspherocytic hemolytic anemia refers to a group of conditions for which the main feature is the premature destruction of red blood cells. Red blood cells move oxygen throughout the body. Premature destruction of red blood cells is called hemolytic anemia. “Nonspherocytic” means the red blood cells are not sphere-shaped like normal red blood cells, and “hereditary” means the conditions are inherited. There are over 16 conditions that fall under the category of hereditary nonspherocytic hemolytic anemia, but they all share these common features. For some people, symptoms are present at birth, but for others, symptoms do not appear until adulthood.
The most common forms of hereditary nonspherocytic hemolytic anemia are G6PD deficiency (https://rarediseases.org/rare-diseases/glucose-6-phosphate-dehydrogenase-deficiency/) and pyruvate kinase deficiency (https://rarediseases.org/rare-diseases/pyruvate-kinase-deficiency/).
Symptoms
People with hereditary nonspherocytic hemolytic anemia may experience yellowing of the skin (jaundice), tiredness, a large spleen (splenomegaly) and/or liver (hepatomegaly).
Lab findings
People with anemia may have the following results in bloodwork: increase in immature red blood cells (reticulocytosis), decrease in mature red blood cells (anemia), increased lactate dehydrogenase and increased bilirubin.
Hereditary nonspherocytic hemolytic anemias are inherited disorders, meaning they are caused by a harmful change (mutation) in a specific gene. Many different genes can cause different types of hereditary anemia. The specific gene involved determines the exact type of anemia a person has, and how it is inherited. A mutation can cause a gene to not work properly, meaning the person’s body does not produce enough of related protein. In some anemias, this leads to a fragile membrane, or outer layer, of the red blood cells, causing the cells to die more quickly. In other types of anemia, the gene change causes a problem with the way red blood cells get the energy they need to function properly. Some people with a non-working gene only have symptoms of hereditary nonsphyrocytic hemolytic anemia after a trigger, such as an illness, taking a certain medication or eating specific foods.
Some forms of hereditary nonsphyrocytic hemolytic anemia are inherited as recessive disorders. Recessive genetic disorders occur when a person inherits a non-working gene from each parent. If a person receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The chance for two carrier parents to both pass on the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
Other types of anemia are inherited as dominant conditions. Dominant genetic conditions occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a new gene change in that person. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
There are some types of hereditary nonspherocytic hemolytic anemia that are X-linked disorders. X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest mostly in males. Females that have a non-working gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the non-working gene. Males have only one X chromosome that is inherited from their mother, and a Y chromosome that is inherited from their father. If a male inherits an X chromosome that contains a non-working gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son. If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
The most common form of hereditary nonspherocytic hemolytic anemia, G6PD deficiency, is thought to affect 400 million people worldwide. In general, hereditary nonspherocytic hemolytic anemias affect more males than females.
A diagnosis of hereditary nonspherocytic hemolytic anemia can be made based on results from a person’s bloodwork. Using a microscope to look at the membrane, or outer layer, of a red blood cell can determine what type of anemia a person has. Genetic testing can also help determine the exact type of anemia. Genetic testing is often done as a multigene panel, which is one test that can look for changes in multiple genes. Genetic counseling can be helpful to better understand genetic testing options, as well as how the condition is inherited, and the impact on family members.
Treatment
For some people with hereditary nonspherocytic hemolytic anemia, symptoms are mild, and no specific treatment is needed. Others require regular blood transfusions to replace red blood cells. People should avoid any drugs or foods that trigger their anemia, such as certain antibiotics. For some people with severe anemia, removal of the spleen (splenectomy) is considered. However, splenectomy can have complications, and is not appropriate for all types of hereditary nonspherocytic hemolytic anemia.
Stem cell therapy is currently being researched for multiple types of hereditary anemia. Stem cells are a type of “baseline” cell that can develop into any other type of cell in the body. Stem cell therapy is not appropriate for all types of hereditary nonspherocytic hemolytic anemia.
Information on current clinical trials is posted on the internet at https://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 NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Grace RF, Glader B. Red blood cell enzyme disorders. Pediatric Clinics of North America. 2018;65(3):579-595. doi:10.1016/j.pcl.2018.02.005.
Kim Y, Park J, Kim M. Diagnostic approaches for inherited hemolytic anemia in the genetic era. Blood Research. 2017;52(2):84-94. doi:10.5045/br.2017.52.2.84.
Haley K. Congenital hemolytic anemia. Medical Clinics of North America. 2017;101(2):361-374. doi:10.1016/j.mcna.2016.09.008.
Koralkova P, Solinge WWV, Wijk RV. Rare hereditary red blood cell enzymopathies associated with hemolytic anemia – pathophysiology, clinical aspects, and laboratory diagnosis. International Journal of Laboratory Hematology. 2014;36(3):388-397. doi:10.1111/ijlh.12223.
Hamilton JW, Jones FG, McMullin MF. Glucose-6-phospahate dehydrogenase Guadalajara:a case of chronic nonspherocytic hemolytic anemia responding to splenectomy and the role of splenectomy in this disorder. Hematology. 2004;9:307-09.
INTERNET
Glucose-6-phosphate dehydrogenase deficiency. Genetics Home Reference. Reviewed May 2017.https://ghr.nlm.nih.gov/condition/glucose-6-phosphate-dehydrogenase-deficiency Accessed July 21, 2020.
Pyruvate kinase deficiency. Genetics Home Reference. Reviewed April 2012.https://ghr.nlm.nih.gov/condition/pyruvate-kinase-deficiency Accessed July 21, 2020. Accessed July 21, 2020.
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