IllnessAutoimmune hemolytic anemia; differential diagnosis

NGS +

Autoimmune lymphoproliferative syndrome (ALPS) is a hereditary disease in which the lymphocyte count is unregulated. ALPS is characterised by lymphoproliferation with lymphadenopathy, hepatomegaly and splenomegaly. Autoimmune disorders are common in ALPS, such as in particular autoimmune hemolytic anemia, autoimmune neutropenia and autoimmune thrombocytopenia. ALPS can cause various symptoms. Often lymphocytes proliferate in childhood, the lymph nodes and spleen are enlarged. The autoimmune disorders mentioned above then typically develop several years later, most commonly as a combination of hemolytic anemia and thrombocytopenia (the so-called Evans syndrome). People with this classic form of ALPS usually have a near-normal life expectancy, but with a greatly increased risk of developing lymphoma. Mutations in the FAS gene cause classic ALPS in ̴75% of affected individuals. The FAS protein is involved in apoptosis. FAS gene mutations result in abnormal protein that impedes apoptosis. As a result, lymphocytes accumulate, leading to autoimmune diseases. Lymphomas may develop when apoptosis is impaired. In most ALPS patients, including those with FAS gene mutations, the disease is inherited in an autosomal dominant manner; rarely, ALPS is inherited in an autosomal recessive manner. Because the diagnostic yield using molecular genetics is unknown, negative DNA test results cannot exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1108/

• Alias: Autoimmune haemolytic anaemia, AIHA
• Allelic: Celiac disease, susceptibility to, 3 (CTLA4)
• Allelic: Diabetes mellitus, insulin-dependent, 12 (CTLA4)
• Allelic: Dyschromatosis symmetrica hereditaria (ADAR)
• Allelic: Dystonia 9 (SLC2A1)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Allelic: Hashimoto thyroiditis (CTLA4)
• Allelic: Juvenile myelomonocytic leukemia (CBL)
• Allelic: Lung cancer, susceptibility to (FASLG)
• Allelic: Myocardial infarction, susceptibility to (GCLC)
• Allelic: Neurodevelopmental disorder with visual defects + brain anomalies (HK1)
• Allelic: Neuropathy, hereditary motor + sensory, Russe type (HK1)
• Allelic: Polymicrogyria [MONDO:0000087, panelapp] (ENO1)
• Allelic: Resistance to malaria due to G6PD deficiency (G6PD)
• Allelic: Retinitis pigmentosa 79 (HK1)
• Allelic: Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Allelic: Systemic lupus erythematosus, susceptibility to (CTLA4)
• Allelic: Wiskott-Aldrich syndrome (WAS)
• Adenosine triphosphate, elevated, of erythrocytes (PKLR)
• Aicardi-Goutieres syndrome 6 (ADAR)
• Anemia, hemolytic, Rh-null, regulator type (RHAG)
• Anemia, hemolytic, due to UMPH1 deficiency (NT5C3A)
• Autoimmune lymphoproliferative syndrome (FAS)
• Autoimmune lymphoproliferative syndrome, type IA (FAS)
• Autoimmune lymphoproliferative syndrome, type IB (FASLG)
• Autoimmune lymphoproliferative syndrome, type II (CASP10)
• Cardiofaciocutaneous syndrome 2 (KRAS)
• Combined cellular and humoral immune defects with granulomas (RAG1)
• Cytopenias and congenital anaemias (ENO1)
• Enolase alpha deficiency (ENO1)
• Erythrocytosis, familial, 8 (BPGM)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Glutathione synthetase deficiency (GSS)
• Hemolytic anemia due to adenylate kinase deficiency (AK1)
• Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (GCLC)
• Hemolytic anemia due to glutathione peroxidase deficiency (GPX1)
• Hemolytic anemia due to glutathione reductase deficiency (GSR)
• Hemolytic anemia due to glutathione synthetase deficiency (GSS)
• Hemolytic anemia due to hexokinase deficiency (HK1)
• Hemolytic anemia due to triosephosphate isomerase deficiency (TPI1)
• Hemolytic anemia, G6PD deficient, favism (G6PD)
• Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency (GPI)
• Immune dysregulation with autoimmunity, immunodeficiency, lymphoproliferation (CTLA4)
• Immunodeficiency 14A, AD (PIK3CD)
• Immunodeficiency 14B, AR (PIK3CD)
• Immunodeficiency, XL, with hyper-IgM (CD40LG)
• Immunodeficiency, common variable, 8, with autoimmunity (LRBA)
• Immunodysregulation, polyendocrinopathy + enteropathy, XL (FOXP3)
• Neutropenia, severe congenital, XL (WAS)
• Noonan syndrome 3 (KRAS)
• Noonan syndrome-like disorder +/- juvenile myelomonocytic leukemia (CBL)
• Omenn syndrome (RAG1)
• Overhydrated hereditary stomatocytosis (RHAG)
• Phosphoglycerate kinase 1 deficiency (PGK1)
• Pyruvate kinase deficiency (PKLR)
• RAS-associated autoimmune leukoproliferative disorder (KRAS)
• Roifman-Chitayat syndrome, digenic (PIK3CD)
• Severe combined immunodeficiency, B cell-negative (RAG1)
• Thrombocytopenia, XL (WAS)
• Thrombocytopenia, XL, intermittent (WAS)
• a/b T-cell lymphopenia with g/d T-cell expansion, severe CMV infection/autoimmunity (RAG1)