Your browser does not support javascript:   Search for gard hereSearch for news-and-events here.

Diseases

Genetic and Rare Diseases Information Center (GARD)

Print friendly version

Hemophagocytic lymphohistiocytosis

Información en español

Other Names for this Disease

  • Familial erythrophagocytic lymphohistiocytosis
  • Familial hemophagocytic lymphohistiocytosis
  • Familial histiocytic reticulosis
  • FHL
  • HLH
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

My 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?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

Is hemophagocytic lymphohistiocytosis inherited?

Hemophagocytic lymphohistiocytosis (HLH) may be inherited or acquired (due to non-genetic factors).

Familial HLH is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a change (mutation) in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two 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% chance to not have the condition and not be a carrier.

Acquired HLH is not inherited. The non-genetic causes of HLH include: infection, medications that suppress the immune system, autoimmune diseases, immunodeficiencies, certain types of cancer and/or metabolic diseases.[2][3]
Last updated: 11/10/2014

Can the older siblings of a child with familial hemophagocytic lymphohistiocytosis develop this condition?

Signs and symptoms of familial hemophagocytic lymphohistiocytosis usually appear within the first few months or years. However, in rare cases, a person may not develop features of the condition until later in childhood or even into adulthood.[1][4][5] Affected siblings usually begin having symptoms at around the same age, although different ages of onset and later onset are possible.[5]

Because familial hemophagocytic lymphohistiocytosis 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. Genetic testing for at-risk relatives is possible if the two disease-causing mutations in the family are known.[1]
Last updated: 11/10/2014

Is genetic testing available for hemophagocytic lymphohistiocytosis?

Yes. Clinical genetic testing is available for the four genes known to cause familial hemophagocytic lymphohistiocytosis, types 2-5. Carrier testing for at-risk relatives and prenatal testing are possible if the two disease-causing mutations in the family are known. Molecular genetic testing is not available for familial hemophagocytic lymphohistiocytosis, type 1 because the genetic cause is currently unknown.[1]

Genetic testing is not available for acquired HLH because it is caused by non-genetic factors.

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Last updated: 11/10/2014

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 6/5/2014

References
  • Kejian Zhang, MD, MBA, Alexandra H Filipovich, MD, Judith Johnson, MS, Rebecca A Marsh, MD, and Joyce Villanueva, MT, MBA.. Hemophagocytic Lymphohistiocytosis, Familial. GeneReviews. January, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1444/. Accessed 11/7/2014.
  • George MR.. Hemophagocytic lymphohistiocytosis: review of etiologies and management.. J Blood Med. June 2014; 5:69-86. Accessed 11/9/2014.
  • Janka GE, Lehmberg K.. Hemophagocytic lymphohistiocytosis: pathogenesis and treatment.. Hematology Am Soc Hematol Educ Program. 2013; 2013:605-611. Accessed 11/10/2014.
  • Kenneth L McClain, MD, PhD. Clinical features and diagnosis of hemophagocytic lymphohistiocytosis. UpToDate. August 27, 2014;
  • 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.
Other Names for this Disease
  • Familial erythrophagocytic lymphohistiocytosis
  • Familial hemophagocytic lymphohistiocytosis
  • Familial histiocytic reticulosis
  • FHL
  • HLH
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.