Cytoband (human 10q22.1 PRF1) & (mouse 10qB4 Prf1).
Here I present: “Hemophagocytic Lymphohistiocytosis“, Victor McKusick, Mendelian Inheritance in Man’, 1966. (PFR1) icd10=D76.1
Hemophagocytic lymphohistiocytosis (HLH) is a severe, potentially fatal syndrome of immune system overactivation, causing a “cytokine storm” where immune cells attack the body’s own blood cells, leading to high fevers, enlarged organs (liver, spleen, lymph nodes), low blood counts, and organ failure. It can be genetic (primary) or triggered by infections, cancers, or autoimmune diseases (secondary) and requires urgent treatment with immunosuppression and chemotherapy to control the inflammation.
What it is
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A hyperinflammatory condition where the immune system becomes dysregulated, leading to excessive activation and proliferation of lymphocytes and macrophages.
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These activated cells engulf other blood cells (hemophagocytosis), causing cytopenias (low blood cell counts) and releasing massive amounts of cytokines, causing widespread inflammation and tissue damage.
Types
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Primary (Familial) HLH:Inherited genetic mutations cause the condition, usually presenting in infancy or early childhood.
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Secondary HLH: An acquired response to triggers like infections (viruses, bacteria), malignancies (lymphoma, leukemia), autoimmune disorders, or rheumatologic conditions, often seen in adults.
Common signs and symptoms
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High, persistent fever
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Enlarged liver, spleen (hepatosplenomegaly)
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Swollen lymph nodes
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Easy bruising, bleeding, or pale skin (due to low platelets/red blood cells)
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Rash
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Neurological changes: irritability, headaches, seizures, poor muscle control
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Failure to thrive or feeding problems (in infants)
Treatment
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Immediate goal: Suppress the hyperactive immune system.
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Medications:Immunosuppressants, corticosteroids, chemotherapy, and specific cytokine-blocking drugs.
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Supportive care: Blood transfusions, managing infections.
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Stem Cell Transplant: May be necessary for severe or primary cases.
Outlook
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Life-threatening, but often treatable with prompt diagnosis and aggressive treatment, with survival rates improving.
There is evidence that hemophagocytic lymphohistiocytosis is caused by mutation in the gene perforin-1 (PRF1) encoded on genomic coordinate 10:70,597,348 and cytoband 10q22.1 in humans.
