Primary immunodeficiency disorders 2

What chromosomal deletion causes DiGeorge syndrome?

22q11.2 deletion

Which branchial pouches are affected in DiGeorge syndrome?

Third and fourth

What are the major clinical features of DiGeorge syndrome?

CATCH-22

What does CATCH stand for in DiGeorge syndrome?

Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia

What causes hypocalcemia in DiGeorge syndrome?

Hypoparathyroidism

When does DiGeorge syndrome usually present?

Neonatal period

What causes tetany and seizures in DiGeorge syndrome?

Hypocalcemia

What facial abnormalities are seen in DiGeorge syndrome?

Low-set ears and fish mouth

What radiographic finding is characteristic of DiGeorge syndrome?

Absent thymic shadow

Which infections are common in DiGeorge syndrome?

Viral and fungal infections

Which viruses commonly infect DiGeorge patients?

CMV, EBV, Varicella

Which fungi commonly infect DiGeorge patients?

Pneumocystis and Candida

What treatment can be used for DiGeorge syndrome?

Thymic graft

Why are older thymic grafts avoided in DiGeorge syndrome?

GVHD risk

Why are live vaccines contraindicated in severe DiGeorge syndrome?

Progressive infection

What immunoglobulin pattern is seen in Hyper-IgM syndrome?

High IgM, low IgG, IgA, IgE

What molecule is defective in Hyper-IgM syndrome?

CD40L

Which cells express CD40L?

CD4 T cells

What process is defective in Hyper-IgM syndrome?

Class switching

Why do patients with Hyper-IgM syndrome still produce IgM?

T-independent response intact

What structure fails to form in Hyper-IgM syndrome?

Germinal centers

Which infections are common in Hyper-IgM syndrome?

Pyogenic infections

What is the treatment for Hyper-IgM syndrome?

IV immunoglobulin

What does SCID stand for?

Severe combined immunodeficiency

What are the classic manifestations of SCID?

Infections, diarrhea, dermatitis, failure to thrive

By what age does SCID usually present?

3 months

Which lymphocytes are defective in SCID?

T cells

Which additional cells may be affected in SCID?

B cells and NK cells

What chest X-ray finding is seen in SCID?

Absent thymus

What is the definitive treatment for SCID?

Bone marrow transplant

How many genes can cause SCID?

More than 15

How is SCID broadly classified?

With or without B cells

What is the T-cell status in SCID?

T-

What inheritance patterns occur in SCID?

X-linked or autosomal recessive

What defect causes X-linked SCID?

Common gamma chain defect

Which interleukin receptors use the common gamma chain?

IL-2, IL-4, IL-7, IL-9, IL-15, IL-21

What lymphocyte phenotype is seen in X-linked SCID?

T- B+ NK-

Loss of IL-2 receptor causes what defect?

Impaired T-cell proliferation

Loss of IL-4 receptor causes what defect?

No IgE class switching

Loss of IL-7 receptor causes what defect?

Loss of T-cell selection

Loss of IL-15 receptor causes what defect?

Absent NK cells

What enzyme deficiency causes autosomal recessive SCID with toxic dATP accumulation?

ADA deficiency

What accumulates in ADA deficiency?

dATP

How does dATP cause immunodeficiency?

Blocks lymphocyte proliferation

What lymphocyte phenotype is seen in ADA deficiency?

T- B- NK+/-

What kinase deficiency resembles X-linked SCID?

JAK3 deficiency

What lymphocyte phenotype is seen in JAK3 deficiency?

T- B+ NK-

What protein is defective in ZAP-70 deficiency?

Tyrosine kinase

Which T cells are absent in ZAP-70 deficiency?

CD8 T cells

What type of CD4 cells are present in ZAP-70 deficiency?

Nonfunctional CD4 cells

What are the features of reticular dysgenesis?

Agranulocytosis with absent T and B cells

What genes are mutated in some cases of SCID with absent T and B cells?

RAG1 and RAG2

What lymphocyte phenotype is seen in RAG deficiency?

T- B- NK+

What lymphocyte phenotype is seen in Ligase 4 deficiency?

T- B- NK+

What is the inheritance pattern of Ataxia-Telangiectasia?

Autosomal recessive

Which gene is mutated in Ataxia-Telangiectasia?

ATM gene

What type of DNA damage is repaired by ATM?

Double-strand breaks

What neurologic manifestation is characteristic of Ataxia-Telangiectasia?

Cerebellar ataxia

What vascular lesion is characteristic of Ataxia-Telangiectasia?

Telangiectasia

Where are telangiectasias commonly found in Ataxia-Telangiectasia?

Eyes and face

What infections are common in Ataxia-Telangiectasia?

Sinopulmonary infections

What radiation sensitivity is seen in Ataxia-Telangiectasia?

X-ray hypersensitivity

What cancer risk is increased in Ataxia-Telangiectasia?

Malignancy

What type of immunity is defective in Ataxia-Telangiectasia?

Cell-mediated immunity

What happens to T-cell function in Ataxia-Telangiectasia?

Reduced

What happens to T- and B-cell numbers in Ataxia-Telangiectasia?

Low

How do patients with Ataxia-Telangiectasia respond to mitogens?

Poorly

What immunoglobulin pattern is seen in Ataxia-Telangiectasia?

Low IgA, normal-high IgM

What inheritance pattern does Wiskott-Aldrich syndrome follow?

X-linked

What cytoskeletal process is defective in Wiskott-Aldrich syndrome?

Actin assembly

What cellular functions are impaired in Wiskott-Aldrich syndrome?

Migration and signaling

What is the triad of Wiskott-Aldrich syndrome?

Thrombocytopenia, infections, eczema

What mnemonic summarizes Wiskott-Aldrich syndrome?

TIE

What causes petechiae in Wiskott-Aldrich syndrome?

Thrombocytopenia

What immunoglobulin pattern is seen in Wiskott-Aldrich syndrome?

Low IgM, high IgA and IgE

How are T-cell numbers affected in Wiskott-Aldrich syndrome?

Normal numbers

How are T-cell functions affected in Wiskott-Aldrich syndrome?

Reduced

Which antigen response is poor in Wiskott-Aldrich syndrome?

Polysaccharide antigens

Which bacteria are poorly recognized in Wiskott-Aldrich syndrome?

Pneumococci

Which infections are common in Wiskott-Aldrich syndrome?

Pyogenic respiratory infections

What is another name for Bare Lymphocyte Syndrome?

MHC deficiency

What is defective in Type I Bare Lymphocyte Syndrome?

MHC class I

What is the consequence of MHC class I deficiency?

No intracellular antigen presentation

What are the clinical features of Type I Bare Lymphocyte Syndrome?

Respiratory infections and skin ulcers

What is defective in Type II Bare Lymphocyte Syndrome?

MHC class II

What causes Type II Bare Lymphocyte Syndrome?

Transcription factor mutations

Why are MHC class II molecules important?

CD4 maturation

What happens to CD4 T cells in Type II Bare Lymphocyte Syndrome?

Marked decrease

How do patients with Type II Bare Lymphocyte Syndrome present?

Like SCID

What does HLH stand for?

Hemophagocytic lymphohistiocytosis

What type of syndrome is HLH?

Hyperinflammatory syndrome

What are the two forms of HLH?

Primary and secondary

Which cells are defective in HLH?

CD8 T cells and NK cells

What protein is commonly mutated in HLH?

Perforin

What cytokine is excessively produced in HLH?

IFN-gamma

What cells become excessively activated in HLH?

Macrophages

What infections commonly trigger HLH?

Viral infections

What are the major clinical features of HLH?

Fever, cytopenias, hepatosplenomegaly

Which inflammatory marker is elevated in HLH?

Ferritin

What neurologic manifestations may occur in HLH?

Neurologic symptoms