Other Names for this Disease
- Familial erythrophagocytic lymphohistiocytosis
- Familial hemophagocytic lymphohistiocytosis
- Familial histiocytic reticulosis
- Hemophagocytic lymphohistiocytosis familial -1
Your QuestionMy granddaughter had familial hemophagocytic lymphohistiocytosis when she was 8 months old. Can her brothers also develop this disease? I have noticed that both of the boys have had skin problems but the older one, now 13, has developed asthma and unexplained headaches. My granddaughter received a BMT from the 2nd born who is now 11 years old. Is there any testing we can have done to check the boys for the presence or absence of the disease?
We have identified the following information that we hope you find helpful. If you still have questions, please contact us.
Questions on this page
Familial hemophagocytic lymphohistiocytosis (FHL) is inherited in an autosomal recessive manner. This means that 2 mutated copies of the disease-causing gene (one inherited from each parent) are necessary to cause the condition. The parents of an individual with an autosomal recessive condition typically carry one mutated copy of the gene and are referred to as carriers. When 2 carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% risk to not have the condition and not be a carrier.
Secondary HLH is not inherited and is usually associated with:
- infection (particularly involving the herpes virus group, usually in older children and adolescents)
- macrophage activation syndrome (MAS), the most serious and life-threatening complication of systemic-onset juvenile idiopathic arthritis (sJIA)
- autoimmune diseases, such as rheumatologic disorders, treated with immune suppressive agents
Secondary HLH is difficult to distinguish from familial HLH by clinical or histologic findings alone. Genetic testing is typically recommended even in HLH that is suspected to be acquired.
Because FHL is inherited in an autosomal recessive manner, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once a sibling at risk is known to be unaffected, the risk of his/her being a carrier is 2/3.
If an affected individual has had genetic testing and the disease-causing mutations have been identified, testing for relatives at risk for either being affected or being carriers is available.
GeneTests lists the names of laboratories that are performing genetic testing for FHL. To view the contact information for the clinical laboratories conducting testing, click here and then click on "Testing" for each type of FHL. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families. Therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.
The following online resources can help you find a genetics professional in your community:
- The National Society of Genetic Counselors provides a searchable directory of US and international genetic counseling services.
- The American College of Medical Genetics has a searchable database of US genetics clinics.
- The University of Kansas Medical Center provides a list of US and international genetic centers, clinics, and departments.
- The American Society of Human Genetics maintains a database of its members, which includes individuals who live outside of the United States. Visit the link to obtain a list of the geneticists in your country, some of whom may be researchers that do not provide medical care.
- Kejian Zhang, Alexandra H Filipovich, Judith Johnson, Rebecca A Marsh, and Joyce Villanueva. Hemophagocytic Lymphohistiocytosis, Familial. GeneReviews. September 7, 2010; http://www.ncbi.nlm.nih.gov/books/NBK1444/. Accessed 11/26/2012.
- Kenneth L McClain. Hemophagocytic lymphohistiocytosis. UpToDate. 2012; http://www.uptodate.com/contents/hemophagocytic-lymphohistiocytosis. Accessed 11/26/2012.
- Rita Clementi, et al. Adult onset and atypical presentation of hemophagocytic lymphohistiocytosis in siblings carryingPRF1 mutations. Blood. September 15, 2002; 100(6):2266. http://bloodjournal.hematologylibrary.org/content/100/6/2266.full. Accessed 11/26/2012.
- Familial hemophagocytic lymphohistiocytosis. Genetics Home Reference. January 2011; http://ghr.nlm.nih.gov/condition/familial-hemophagocytic-lymphohistiocytosis. Accessed 11/26/2012.