Hemolytic Anemia

 

Autoimmune Lymphoproliferative Syndrome

 

Autoimmune Lymphoproliferative Syndrome (ALPS) - This disease is characterized by defective activation induced cell death which leads to uncontrolled lymphoproliferation.  Patients develop hepatosplenomegaly, adenopathy, and autoimmune cytopenias (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, autoimmune neutropenia).  

CVID

 

CVID - Approximately 25% of patients develop autoimmune disease.  Autoimmune hemolytic anemia and ITP are the most frequently reported conditions.  

 

 

AID Deficiency

 

AID deficiency - Patients develop autoimmune manifestations at high frequency (approximately 25%).  These include hemolytic anemia, thrombocytopenia, and autoimmune hepatitis. 
  

IgA Deficiency

 

IgA deficiency - Patients have an increased incidence of autoimmune disease including juvenile idiopathic arthritis, SLE, vitiligo, hemolytic anemia, ITP, and thyroiditis.  Most patients with IgA deficiency do not have recurrent infections.
  

IPEX

 

IPEX - Approximately one-half of patients with this syndrome develop autoimmune cytopenias including coombs positive hemolytic anemia, ITP, and autoimmune neutropenia.  

 

Wiskott-Aldrich Syndrome

 

Wiskott-Aldrich syndrome - Autoimmune disorders have been reported in 40% of patients.  These include hemolytic anemia, autoimmune neutropenia, skin and cerebral vasculitis, arthritis, renal disease, and Henoch-Schonlein purpura. 

 

MHC Class II Deficiency

 

MHC Class II Deficiency - Autoimmune cytopenias (hemolytic anemia, neutropenia) have been described in 10% of patients. 

 

PNP Deficiency

 

Purine Nucleoside Phosphorylase (PNP) deficiency - Patients develop a number of autoimmune manifestations including hemolytic anemia, ITP, and autoimmune neutropenia.  Less common manifestations include SLE and CNS vasculitis.  

 

Kabuki Syndrome

 

Kabuki syndrome - Autoimmune hemolytic anemia and ITP have been reported in this disease. 

 

Cartilage Hair Hypoplasia

 

Cartilage Hair Hypoplasia - Patients can develop autoimmune manifestations such as hemolytic anemia, ITP, juvenile idiopathic arthritis, and autoimmune enteropathy. 

 

Cernunnos Deficiency

 

Cernunnos deficiency - Two patients with autoimmune hemolytic anemia and ITP have been reported.  

 

G6PD Deficiency

 

Glucose-6-phosphate-dehydrogenase (G-6PD) deficiency - Patients develop hemolytic anemia.  Decreased G-6PD function leads to a reduction in NADPH (which protects erythrocytes from oxidative stress).  If the G-6PD activity is below 5%, the oxidative burst of phagocytes is also severely impaired (NBT test and dihydrodhodamine assay will be abnormal) and patients develop CGD-like infections. 

 

CTLA4 Deficiency

 

CTLA4 Deficiency - patients develop multi-organ autoimmune manifestations including inflammatory bowel disease,autoimmune cytopenia, psoriasis, and thyroid disease. Patients also develop splenomegaly, hepatomegaly, bronchiectasis, GLILD, and generalized lymphadenopathy.

 

LRBA Deficiency

 

LRBA Deficiency - patients develop multi-organ autoimmune manifestations including inflammatory bowel disease,autoimmune cytopenia, psoriasis, and thyroid disease. Patients also develop splenomegaly, hepatomegaly, bronchiectasis, GLILD, and generalized lymphadenopathy.

 

PIK3CD Gain of Function

 

PIK3CD Gain of Function - patients develop autoimmune manifestations including inflammatory bowel disease, autoimmune cytopenia, and autoimmune primary sclerosing cholangitis. Patients may also develop EBV/CMV induced lymphoproliferation, hepatosplenomegaly and malignancy (lymphoma).

 

STAT3 Gain of Function

 

STAT3 Gain of Function - patients develop multi-organ autoimmune manifestations including autoimmune enteropathy autoimmune cytopenia, type I diabetes, and interstitial lung disease.