Resources on PID

Disease Contributors Clinical criteria for a probable diagnosis (= clinical diagnosis) Suggestions for alternative diagnosis (i.e. if these criteria are not completely fulfilled)
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)
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
Bloom syndrome Markus Seidel, Beata Wolska, Corry Waemes, Andy Gennery Short stature
• 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
Cartilage hair hypoplasia (CHH) Nizar Mahlaoui, Bobby Gaspar, Andrew Gennery Short stature
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
no sign of other immune-osseous dysplasia (Schimke disease)
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
Recurrent and/or severe infections
Normal or increased CD4, CD19 and CD56
normal class HLA-class 1 expression
Other primary causes of lymphopenia excluded
DiGeorge syndrome Nizar Mahlaoui David Edgar Stephan Ehl Documented microdeletion 22q11 or 10p
signs of immunodeficiency, i.e. infections (recurrent or severe bacterial) and/or immune dysregulation
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
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)
• 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
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)
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
Nijmegen breakage syndrome Markus Seidel, Beata Wolska, Corry Waemes, Andy Gennery Microcephaly
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
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
Warts hypogammaglobulinem ia infections and myelokathexis (WHIM) Jean Donadieu, Sarah, Beaussant Cohen, Bodo Grimbacher Neutropenia
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
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