Hemophagocytic lymphohistiocytosis (HLH) [51 genes]

Hemophagocytic lymphohistiocytosis is an inflammatory disease that can be lethal. It is characterized by histiocytosis, reduced or absent levels of NK cell activity, and excess release of cytokines.

The severity and progression of untreated patients can lead to early death from uncontrolled invasive infections in most cases. There is a predisposition to suffer EBV infections, although other viruses and bacteria can cause infection. The clinical diagnostic criteria is confirmed by genetic tests, which explain approximately 45% of patients with HLH, and the remaining 55% could be caused by sporadic HLH of complex or multifactorial origin.

• 1/50,000 individuals

The genetic study of HLH provides information to distinguish between a primary cause of HLH and a secondary one.

If a primary HLH is detected, the result of the genetic study provides benefits in terms of the application of specific immunosuppressive therapies that may be available for certain types of familial HLH, as well as genetic counseling associated with the inheritance pattern of the disease.

Diagnostic criteria for HLH include:

• Fever
• Splenomegaly
• Cytopenia in more than two cell lineages
• Hypertriglyceridemia, elevated ferritin levels and sCD25
• Hemophagocytosis in bone marrow, spleen or lymphoid nodes
• Low or absent NKs activity

Reviewed data estimate that approximately 40% of patients with HLH have a molecular diagnosis, with 65% of those patients being less than one year old. However, it is important to highlight that these data come from cohorts with a clinical diagnosis of HLH.