Disease | Contributors | Clinical criteria for a probable diagnosis (= clinical diagnosis) | Suggestions for alternative diagnosis (i.e. if these criteria are not completely fulfilled) |
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Combined immunodeficiency (CID) | Stephan Ehl, Maria Kanariou, Alain Fischer | At least one of: • at least one severe infection (requiring hospitalization) • one manifestation of immune dysregulation (autoimmunity, IBD, severe eczema, lymphoproliferation, granuloma) • malignancy • affected family member AND 2 of 4 T cell criteria fulfilled: • reduced CD3 or CD4 or CD8 T cells (using age-related reference values) • reduced naive CD4 and/or CD8 T cells • elevated g/d T cells • reduced proliferation to mitogen or TCR stimulation AND HIV excluded AND exclusion of clinical diagnosis associated with CID (e.g. defined syndromic diseases, DKC, AT, CHH) |
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Hyper IgE syndrome (HIES) | Beata Wolska, David Edgar, Bodo Grimbacher, Steven Holland | IgE > 10 times the norm for age AND pathologic susceptibility to infectious diseases AND no evidence of T-cell deficiency (low T cell numbers, low naive T cells, reduced proliferation) AND no evidence of B cell deficiency (low B cell numbers, hypogammaglobulinaemia) |
• For patients with evidence of T-cell deficiency, please consider: Combined immunodeficiencies. • For patients with evidence of B-cell deficiency, please consider Unclassified antibody deficiency. • For other patients, please consider Unclassified immunodeficiencies. |
Ataxia telangiectasia (ATM) | Nizar Mahlaoui David Edgar Stephan Ehl, Richard Gatti, Dominique Stoppa-Lyonnet | Ataxia AND at least two of the following : • Oculocutaneous telangiectasia • Elevated alphafetoprotein (tenfold the upper limit of normal) • Lymphocyte A-T caryotype (translocation 7;14) • Cerebellum hypoplasia on MRI |
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Bloom syndrome | Markus Seidel, Beata Wolska, Corry Waemes, Andy Gennery | Short stature AND • immunodeficiency (hypogammaglobulinemia, variably reduced lymphocyte proliferation, lower respiratory tract infections) • Cytogenetics: high sister-chromatid exchange rate, chromosomal breaks AND at least one of the following • Skin: photosensitivity, butterfly erythema, café-au-lait maculae • Head: microcephaly, dolichocephaly, prominent ears and nose • Hands: syndactyly, polydactyly, fifth finger clinodactyly • Malignoma: leukemia, lymphoma, adenocarcinoma, squamous cell carcinoma |
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Cartilage hair hypoplasia (CHH) | Nizar Mahlaoui, Bobby Gaspar, Andrew Gennery | Short stature AND immunodeficiency (combined immunodeficiency (variable T and B cell lymphopenia), AND AT LEAST one of the following: • radiographical manifestations of CHH (metaphyseal chondrodysplasia, • light-coloured hypoplastic hair / fine silky hair • gastrointestinal malabsorption or Hirschsprung’s , • hematological abnormalities (bone marrow dysplasia, pure red cell aplasia), • granulomatous inflammation (skin lesions,…), • EBV driven lymphoproliferative disease • Malignancies AND no sign of other immune-osseous dysplasia (Schimke disease) |
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CD8 deficiency | Nizar Mahlaoui, Matthew Buckland, Sofia Grigoriadou | CD8+ cells: less than 350/µl if age less than 2 years less than 250/µl if age betweeen 2 and 4 years less than 150/µl if age greater than 4 years AND Recurrent and/or severe infections AND Normal or increased CD4, CD19 and CD56 AND normal class HLA-class 1 expression AND Other primary causes of lymphopenia excluded |
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DiGeorge syndrome | Nizar Mahlaoui David Edgar Stephan Ehl | Documented microdeletion 22q11 or 10p AND signs of immunodeficiency, i.e. infections (recurrent or severe bacterial) and/or immune dysregulation |
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Dyskeratosis congenita | Nizar Mahlaoui David Edgar Stephan Ehl, Inderjeet Dokal | At least two of the following: • Skin pigmentation abnormalities • Nail dystrophy • Mucosal leucoplakia • Bone marrow failure AND Very short telomeres |
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Immunodeficiency centromeric instability facial anomalies syndrome (ICF) | Markus Seidel, Beata Wolska, Corry Waemes, Capucine Picard | Immunodeficiency (variable hypogammaglobulinemia, variably reduced T, B, and NK cells, bacterial and opportunistic infections) AND • Head: microcephaly, hypertelorism, epicanthal folds, flat face, micrognathia, macroglossia, tongue protrusion, small upturned nose • Cytogenetics: Centromeric instability of chromosomes 1, 9 and 16 with increased somatic recombination and formation of multibranched/-radial configurations AND at least two of the following • Short stature • Neurologic: variable mental retardation • Malabsorption, diarrhea • Sinusitis, upper and lower respiratory tract infections |
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Hoyeraal-Hreidarsson syndrome | Nizar Mahlaoui David Edgar Stephan Ehl, Inderjeet Dokal | At least four of the following criteria: • Microcephaly and/or neurocognitive impairment • Cerebellar hypoplasia • Bone marrow failure • Immune deficiency including B cell lymphopenia • Severe enteropathy • Severe failure to thrive This can be substantiated by undertaking telomere length analysis (usually very short) |
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Netherton syndrome | Drafted by Joris van Montfrans reviewed by E. Renner, Hans Ochs and Nizar Mahlaoui | At least two of the following: • generalized ichthyosis (erythroderma covered by fine scales) with an onset < 2 months of age • short hair due to broken off distal shaft, specific hair shaft abnormality called trichorrhexis invaginata or "bamboo hair" • atopic manifestations, including food allergies or elevated serum levels of IgE. AND at least one of the following: • failure to thrive in the first years of life • recurrent infections (skin and other locations) • intermittent diarrhea |
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Nijmegen breakage syndrome | Markus Seidel, Beata Wolska, Corry Waemes, Andy Gennery | Microcephaly AND reduced T cell number and/or elevated percentage of memory CD4 and CD8 cells and/or reduced T cell function AND at least two of the following • Typical facial appearance • Variable hypogammaglobulinemia, dysgammaglobulinemia and/or reduction of B cells - opportunistic and/or chronic, recurrent infections, predominantly of the respiratory tract • Skin: Café-au-lait spots and/or hypopigmented areas and/or skin granulomas • lymphoma/leukemia or other malignancy • Chromosomal instability (especially chrom. 7 and 14), increased sensitivity towards ionizing radiation and alkylating agents |
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Schimke disease | Nizar Mahlaoui David Edgar Stephan Ehl | Predominantly T cell defects (low T cell counts, low T cell proliferations) AND osseous dysplasia (metaphyseal usually) AND kidney dysfunction |
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Warts hypogammaglobulinem ia infections and myelokathexis (WHIM) | Jean Donadieu, Sarah, Beaussant Cohen, Bodo Grimbacher | Neutropenia AND lymphopenia AND monocytopenia AND Evidence of myelokathexis on bone marrow smear; AND at least one of the following: • Recurrent and severe HPV infections • Recurrent bacterial infections • Mycobacterial infection(s). • Mild hypogammagobulinemia |