IllnessSevere Combined Immuno Deficiency, SCID; differential diagnosis

NGS +

Severe combined immune deficiency (SCID) refers to a group of inherited diseases characterized by defects in, both, the T and B lymphocyte responses. Classic symptoms of SCID include increased susceptibility to a variety of infections, including acute otitis media, pneumonia or bronchitis, oral thrush and diarrhea. Because children with SCID go through many infections, they do not thrive - if left untreated, they rarely live past two years of age. The average age at which babies are diagnosed with SCID is usually over 6 months because of recurrent infections and poor growth. The most common form of SCID is called XSCID. Another of the different forms is caused by a deficiency of the enzyme adenosine deaminase (ADA). In ADA SCID, cells are prevented from producing new DNA efficiently. In addition, toxic metabolites are not removed, accumulate and damage lymphocytes. XSCID is caused by mutations in the IL2RG gene, which encodes an activating receptor on the lymphocyte membrane. Stimulated by cytokines, lymphocytes mature, proliferate and are mobilized to fight infections. The different forms of SCID are transmitted according to all classical inheritance patterns. By using a comprehensive gene panel (n>30), almost all genetic cases of SCID can be clarified by DNA testing after thorough clinical characterization of the patient. Currently, the most effective treatment for SCID is bone marrow transplantation from matched sibling donors in the first three months of life.

References: https://www.ncbi.nlm.nih.gov/books/NBK1410/

https://www.ncbi.nlm.nih.gov/books/NBK1483/

• Allelic: Autoimmune disease, multisystem, infantile-onset, 2 (ZAP70)
• Allelic: Hepatitis C virus, susceptibility to (PTPRC)
• Allelic: Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Allelic: IgE, elevated level of (IL21R)
• Allelic: Multiple myeloma, resistance to (LIG4)
• Allelic: Myopathy, tubular aggregate, 1 (STIM1)
• Allelic: Myopathy, tubular aggregate, 2 (ORAI1)
• Allelic: Stormorken syndrome (STIM1)
• Adenosine deaminase deficiency, partial (ADA)
• Allelic: Anauxetic dysplasia 1 (RMRP)
• Allelic: Intellectual developmental disorder dysmorphic face, speech delay, T-cell abnorm (BCL11B)
• Allelic: Metaphyseal dysplasia without hypotrichosis (RMRP)
• B-cell expansion with NFKB + T-cell anergy (CARD11)
• CHARGE syndrome (CHD7)
• Cartilage-hair hypoplasia (RMRP)
• Combined cellular + humoral immune defects with granulomas (RAG1, RAG2)
• Combined immunodeficiencies with associated or syndromic features [panelapp] (RMRP)
• Combined immunodeficiency, XL, moderate (IL2RG)
• Gastrointestinal defects + immunodeficiency syndrome (TTC7A)
• Growth hormone insensitivity with immune dysregulation 1, AR (STAT5B)
• Growth hormone insensitivity with immune dysregulation 2, AD (STAT5B)
• Immunodeficiency 10 (STIM1)
• Immunodeficiency 11A (CARD11)
• Immunodeficiency 11B with atopic dermatitis (CARD11)
• Immunodeficiency 15A (IKBKB)
• Immunodeficiency 15B (IKBKB)
• Immunodeficiency 18 (CD3E)
• Immunodeficiency 18, SCID variant (CD3E)
• Immunodeficiency 19 (CD3D)
• Immunodeficiency 22 (LCK)
• Immunodeficiency 24 (CTPS1)
• Immunodeficiency 25 (CD247)
• Immunodeficiency 26, with/-out neurologic abnormalities (PRKDC)
• Immunodeficiency 48 (ZAP70)
• Immunodeficiency 49, severe combined (BCL11B)
• Immunodeficiency 52 (LAT)
• Immunodeficiency 56 (IL21R)
• Immunodeficiency 73A with defective neutrophil chemotaxix + leukocytosis (RAC2)
• Immunodeficiency 73B with defective neutrophil chemotaxis + lymphopenia (RAC2)
• Immunodeficiency 73C with defective neutrophil chemotaxis + hypogammaglobulinemia (RAC2)
• Immunodeficiency 8 (CORO1A)
• Immunodeficiency 9 (ORAI1)
• Immunodeficiency due to purine nucleoside phosphorylase deficiency (PNP)
• LIG4 syndrome (LIG4)
• Omenn syndrome (RAG1, RAG2, DCLRE1C)
• Omenn syndrome [panelapp] (RMRP)
• Otofaciocervical syndrome 2 (PAX1)
• Reticular dysgenesis (AK2)
• SCID, autosomal recessive, T-negative/B-positive type (JAK3)
• Schimke immunoosseous dysplasia (SMARCAL1)
• Severe combined immunodeficiency + microcephaly, growth retard., sens. to ionizing radiation (NHEJ1)
• Severe combined immunodeficiency due to ADA deficiency (ADA)
• Severe combined immunodeficiency, Athabascan type (DCLRE1C)
• Severe combined immunodeficiency, B cell-negative (RAG1, RAG2)
• Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive (PTPRC)
• Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive (IL7R)
• Severe combined immunodeficiency, XL (IL2RG)
• Sneddon syndrome (ADA2)
• T-cell immunodeficiency, congenital alopecia + nail dystrophy (FOXN1)
• T-cell lymphopenia, infantile, with/-out nail dystrophy, AD (FOXN1)
• Transcobalamin II deficiency (TCN2)
• Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome (ADA2)
• a/b T-cell lymphopenia + g/d T-cell expansion, severe cytomegalovirus infect., autoimmunity (RAG1)