Anna was diagnosed with Familial HLH which means that it is thought to be hereditary.  This diagnosis was made based on Anna's young age at diagnosis (8 weeks), but at this point we have no proof. 

As you will learn below, at this point only two of the expected three or four genetic causes have been identified.  Anna did not have the deficiency of perforin - gene PRF1.  At this time we are in the process of being tested for the second mutation found - Munc 13-4. 

We recently learned that a third mutation has been identified:  Syntaxin 11

The following information was taken from the Histiocytosis Association's web site.  The Histiocytosis web site is the best place for detailed information about HLH.  It also has some great tools to get in contact with other families who are dealing with this disease. 

Please go to www.histio.org for detailed information about HLH.

What is hemophagocytic lymphohistiocytosis?
Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder primarily affecting young children at a very early age, but it is found in patients of all ages.

The human body contains many types of cells which help fight infection. One type of cell is called the histiocyte. Histiocytes are produced by the bone marrow, and they may travel throughout the body. At a later stage, these cells remain in place within various tissues in the body. Their job is to help destroy certain foreign materials and to fight infections. This is done in cooperation with other important cells.

Patients with active HLH have too many of these histiocytes, as well as lymphocytes (another kind of infection-fighting cell), both of which are so-called white blood cells that may cause inflammation (swelling, redness, heat, pain, and loss of function). These cells then begin to penetrate and accumulate in good tissue and can cause damage to a variety of organs.

What causes this disease?
Scientists do not yet know all the complicated processes involved in this disease.

There are two major forms of HLH. One, known as the primary form, is inherited. The other is known as the secondary form. In the secondary form, the disease develops secondary to inappropriate (abnormal) activity of the immune system. This can occur after the use of immunosuppressive therapy and/or infections.

What does familial mean?
Familial hemophagocytic lymphohistiocytosis (also known as FHL, FEL or FHLH) means that the particular form of the disease is genetic.

How will I know if it is familial?
It is extremely difficult, if not impossible, to distinguish by testing between a primary (familial) and secondary form of HLH in each patient. However, onset at an early age is suggestive of a familial form, whereas onset later than 6 years of age is rare in the familial form.

What genes cause familial HLH (FHL)?
Thus far, two of an expected three or four genetic causes of familial HLH have been described. One genetic mutation that causes FHL results in a deficiency of perforin, a critical protein responsible for the function of immune cells involved in control of viral infections. The gene is named PRF1. Perforin is required for natural-killer lymphocytes (NK cells) and T lymphocytes (cytotoxic T cells) to fight viral infections and also to keep the immune system, especially histiocytes, under control. A second genetic mutation responsible for FHL involves the gene-encoding Munc13-4 protein, which is also involved in the function of NK and T cells.