X-linked familial hemophagocytic lymphohistiocytosis; XIAP deficiency; X-linked lymphoproliferative syndrome type 2 (XLP-2)-MAS

Order Genetic Testing


SAID group:
Macrophage Activation Diseases


X-linked. X-linked dominant male inheritance (typical presentation). There are some female carriers with some symptoms. Testing recommended for XIAP (and also SAP) in males with symptoms of HLH after Epstein-Barr virus (EBV) infections, or HLH presenting in childhood or adolescence. [84]



Timing of symptoms:
Onset of HLH may be the first sign of this disease, and may occur after Epstein-Barr infections (that can be severe). [85] Some cases developed pancytopenia and splenomegaly after MMR vaccine. [88]

Age of onset:
Infancy to early childhood. A few with school-age onset. [84] [88]

Skin cutaneous:
Some patients may have erythema nodosum, including female carriers of an XIAP deficiency. [85] One case of recurrent rashes with fevers. [83]

Prolonged, periodic fevers >7 days. [84] A few with pathologic cerebrospinal fluid (CSF). [85]

Uncommon. One case with sensorineural hearing loss in childhood. [83] Hearing loss not noted in other cases. [84] [85]

Uveitis [83] [87]. One case with bilateral cataracts in early childhood. [83]

Severe cases of infectious mononulcleosis leading to HLH is common. [84] [85] Some with increased risk for severe, recurrent or rare respiratory infections. [88]

Higher risk for early-onset inflammatory bowel diseases (Crohns, colitis, IBD), even in female carriers of the XIAP deficiency mutation. [85] Hepatomegaly, splenomegaly, granulomatous hepatitis. [83] [88] Chronic and/or hemorrhagic colitis that can be fatal (one case with portal hypertension). [88] Crohns-like disease, celiac-like disease. [87] Some patients with chronic liver failure and/or hepatitis. [85] Cholangitis (sometimes associated with colitis). [88]

Splenomegaly (may be the first presenting symptom). [88] Hemophagocytic lymphohistiocytosis (HLH) affects 90% of cases [85] and many can have recurrent HLH. HLH can occur after Epstein-Barr virus (EBV). [85] [88] No known patients with lymphoma or aplastic anemia. [84]

Joints bones muscles cartilage:
Uncommon. [84] [85] [88] One case with arthritis in the hips and knees that also developed myositis. [83]

Not noted. [83] [84] [88]

One case with elevated serum amyloid. [83] Not tested in other cases in the literature.

Abnormal labs:
High: ESR, CRP, liver function tests (LFTs), triglycerides, ferritin, [85] IL-18 [86] cytopenia. [85] Low: fibrinogen, platelets, anemia, neutropenia, hemophagocytosis. [88] Normal NK cell function [85] Variable NKT cell defects. [84] IgG normal in untreated patients. [85] Low IgG secondary to treatments. [84] [85]

Search Keywords:
X-linked familial hemophagocytic lymphohistiocytosis, XIAP deficiency, X-linked lymphoproliferative syndrome type 2 (XLP-2)-MAS, vaccine, vaccine triggered, MMR, Measles, XLP2-MAS, XLP-2, macrophage activation, macrophage activation syndrome, MAS, XIAP, BIRC4, lymphohistiocytosis, histiocytosis, hemophagocytic lymphohistiocytosis, HLH, X linked HLH, hemophagocytic lymphohistiocytosis epstein-barr virus, epstein-barr virus, pancytopenia, erythema nodosum, periodic fever, recurrent fever, fever, periodic fever HLH, viral triggered HLH, mono, mononulcleosis, mononulcleosis HLH, mononulcleosis hemophagocytic lymphohistiocytosis, uveitis, cataracts, inflammatory bowel diseases, early onset inflammatory bowel disease, abdominal pain, hepatomegaly, splenomegaly, granulomatous hepatitis, colitis, Crohns, IBD, hemorrhagic colitis, portal hypertension, cholangitis, hepatitis, arthritis, myositis, hepatosplenomegaly, enlarged liver, enlarged spleen, enlarged liver and spleen, large liver, large spleen, large liver and spleen, anemia, amyloid, triglycerides, ferritin, IL-18, cytopenia, high liver function tests, neutropenia, hemophagocytosis, joint pain, leg pain, liver failure, granulomatous hepatitis, granulomatous, Epstein-Barr, EBV, mono, mononucleosis

[ Previous | Next ]

Photo credit:

Photo needed. Contact karen@autoinflammatory.org to submit a photo for this disease.


  • NIH-WRNMMC 2nd Symposium on Autoinflammatory & Immunedysregulatory Diseases Registration is open for this free symposium August 22-23, 2019!

  • Autoinflammatory Patient & Family Program Join us on August 24th for the patient program, with fun, food and talks by doctors that are experts for autoinflammatory diseases.

  • Genetic Testing Our blog post and downloadable pdf of US genetic testing panels for autoinflammatory diseases.

  • saidsupport.org Our blog with the latest news,& helpful information for thriving with an autoinflammatory diseases.

  • Healthier Ever After Our book/program to help kids with injectable medications.

    Print this page