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14 Primary Immunodeficiency Diseases


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14 Primary Immunodeficiency Diseases

  1. 1. Primary Immunodeficiency Diseases ( PID )
  2. 2. Objectives What will I learn? Characteristics of immune development in children classification and clinical manifestation Diagnosis Treatment
  3. 3. D.Deorge Wiskott Aldrich
  4. 4. Case Presentation D. George is a 2 year old male brought in by his parents Wiskott and Aldrich because of concerns about recurrent infections . They state he has been sick many times over the last two years. He has been in the hospital twice with some sort of infection. He has also had frequent upper respiratory infections and has had Otitis Media 7 times in the last two years.
  5. 5. <ul><li>The parents of D. George are very concerned. They wonder is there something wrong with him. </li></ul><ul><li>● Is it normal to have so many infections? </li></ul><ul><li>● Could there be something wrong with his </li></ul><ul><li>immune system? </li></ul><ul><li>● How are you going to figure this out? </li></ul><ul><li>● Does he need testing? </li></ul>
  6. 6. Questions <ul><li>● What other information should we try to get from D. George and the family? </li></ul><ul><li>● Are there clues we could be missing in the history? </li></ul><ul><li>● Are there clues in the physical? </li></ul>
  7. 7. Immunology review (development and features of IM)
  8. 8. Organs of the Immune System
  9. 9. Immune system Specific Nospecific ILs IFNγ TNFα IgM IgG1 ~ 4 IgA1 、 2 IgD 、 IgE phagocytic cells Macrophages (MC/MΦ) Neutrophils T cells B cells ( organs, cells and molecules ) complement system
  10. 10. Immunology Review <ul><li>● Have Lymphoid Progenitor for Lymphocytes </li></ul><ul><ul><li>Becomes T cell in Thymus </li></ul></ul><ul><ul><ul><li>Important in Cellular Immunity </li></ul></ul></ul><ul><ul><ul><li>Develop into CD4, CD8 or other cells </li></ul></ul></ul><ul><ul><ul><li>Secretes cytokines, interleukins, etc. </li></ul></ul></ul><ul><ul><ul><li>Assists B cells in making immunoglobulins </li></ul></ul></ul><ul><ul><li>Becomes B cell in Bone Marrow </li></ul></ul><ul><ul><ul><li>Begins with IgM </li></ul></ul></ul><ul><ul><ul><li>Matures to form other immunoglobulins </li></ul></ul></ul><ul><ul><ul><ul><li>IgA, IgE, or IgG (with subclasses IgG1-4) </li></ul></ul></ul></ul><ul><ul><ul><li>Mature cell is Plasma cell </li></ul></ul></ul><ul><ul><ul><li>Immunoglobulins used to surround antigens for phagocytosis </li></ul></ul></ul><ul><ul><ul><li>Responsible for Specific immunity (and memory) </li></ul></ul></ul>
  11. 11. SL SC ProB CFU MØ PMN Plet RBC PreB PT T THYRUM Epi. BM CD3 + IFN- γ 、 IL-2 IL-4 、 5 、 8 、 9 、 10 、 13 Development of Immune cell B Plasma IgM B Plasma IgA IgA IgM B Plasma IgG IgG B Plasma IgE IgE CD19 + CD20 + CD8 + CD4 + TH1 TH2 CTL
  12. 12. More Immunology Review? <ul><li>● Neutrophils and Macrophages </li></ul><ul><ul><li>Surround and gobble up organisms, often those surrounded by immunoglobulins (Phagocytosis and Opsonization). </li></ul></ul><ul><ul><li>Part of natural or innate or nonspecific immunity. </li></ul></ul><ul><li>● Complement system </li></ul><ul><ul><li>Cascade of plasma proteins which aid in chemotaxis and opsonization. </li></ul></ul>
  13. 14. Characteristic of immune development in children <ul><li>T cell and cytokine </li></ul><ul><li>CTL ↓ —— susceptibility to infections </li></ul><ul><li>T H 2 ↑ —— allergic diseases </li></ul><ul><li>B cell and antibody </li></ul><ul><li>antibody production↓ , all kinds of Ig↓ </li></ul><ul><li>MC/MΦ function insufficient </li></ul><ul><li>PMN function insufficient </li></ul><ul><li>Complement system </li></ul><ul><li>Other immune molecules </li></ul><ul><li>Mannose-binding lectin </li></ul>
  14. 15. Development of Immunoglobulin 6M birth 100% IgG level of Infant IgG from mother IgG of infant
  15. 16. Age dependent changes of serum Igs levels(g/L ) Ages IgG IgA IgM Neonate 6.46-17.74 0.004-0.017 0.05-0.27 1m- 2.75-7.50 0.05-0.60 0.10-0.70 4m- 3.70-8.30 0.14-0.50 0.33-1.25 7m- 3.50-8.90 0.06-0.54 0.36-1.20 1y- 5.52-11.46 0.06-0.74 0.60-2.12 3y- 4.95-12.74 0.33-0.89 0.65-2.01 7y- 6.09-12.85 0.52-2.16 0.67-2.46 12y- 6.98-14.26 0.92-2.50 0.56-2.18 15-18y 7.54-16.02 0.89-3.24 0.72-2.28
  16. 17. Schematic diagram of the exposure of microorganism during early life fetus Full tern 6M Day care pathogens probiotics
  17. 18. Period of susceptible children premature Full term 6M Day care
  18. 19. Prevalence <ul><li>● “ The first cause of recurrent infections in children is childhood itself.” </li></ul><ul><li>● Average number of infections is 6-8 URI’s per year. </li></ul><ul><li>● Common triggers for more frequent URI’s. </li></ul><ul><ul><li>Daycare </li></ul></ul><ul><ul><li>Smoking </li></ul></ul><ul><ul><li>Allergies and asthma </li></ul></ul>
  19. 20. Prevalence <ul><li>Most children with recurrent infections don’t have primary immunodeficiency </li></ul><ul><ul><li>90% have secondary cause </li></ul></ul>
  20. 21. Secondary Causes of Recurrent Infections <ul><li>HIV, HIV, and HIV </li></ul><ul><li>Anatomic </li></ul><ul><ul><li>Foreign Body </li></ul></ul><ul><ul><li>Central line </li></ul></ul><ul><ul><li>Eustacian Tube Obstruction </li></ul></ul><ul><ul><li>Sinus tract/fistula </li></ul></ul><ul><ul><li>Sacral Dimple </li></ul></ul><ul><ul><li>Cribiform Plate Disruption </li></ul></ul><ul><ul><li>Lung sequestration </li></ul></ul><ul><ul><li>Hypotonia causing aspiration </li></ul></ul><ul><ul><li>Vesicoureteral Reflux </li></ul></ul><ul><li>Medications </li></ul><ul><li>Allergy or Asthma </li></ul><ul><li>Cystic Fibrosis </li></ul><ul><li>GERD </li></ul><ul><li>Malnutrition </li></ul><ul><li>Sickle Cell </li></ul><ul><li>Asplenia </li></ul><ul><li>Diabetes </li></ul><ul><li>Cancer </li></ul><ul><li>Colonization with resistant organism (i.e. MRSA) </li></ul>
  21. 22. Primary Immunodeficiency Disease <ul><li>A group of disorders characterized by an impaired ability to produce normal immune response. Most of these disorders are caused by mutations in genes involved in the development and function of immune organs, cells, and molecules. </li></ul><ul><li>Clinical features : Recurrent infection , high risk of autoimmune diseases, allergy and malignancy </li></ul>
  22. 23. 50% 20% 10% 18% 2% Antibody Complement Phagocyte Cell medi ated Combined Distribution of PID Up to 2007 more then 200 kinds of PID reported
  23. 25. Classification(new) <ul><li>Combined Immunodeficiency (B and T cells) </li></ul><ul><li>Predominantly antibody deficiency (B cells and Ab) </li></ul><ul><li>Predominantly T-cell deficiency (T cells) </li></ul><ul><li>Immunodeficiency syndromes </li></ul><ul><li>Phagocyte deficiency ( PMN’s) </li></ul><ul><li>Complement deficiency </li></ul><ul><li>Others </li></ul><ul><li>Note :-- There is significant overlap among syndromes. </li></ul><ul><li>--Great variability in expression of disorders for all categories </li></ul><ul><li>from mild to severe/fatal. </li></ul>
  24. 26. Combined immunodeficiencies ( 1 ) 1. Severe combined immunodeficiency ( SCID ) X-linked (γc deficiency) Autosomal recessive (Jak3 deficiency) RAG1/RAG2 deficiency Adenosine deaminase (ADA) deficiency Reticular dysgenesis T – B + T - B -
  25. 27. Severe Combined Immunodeficiency , SCID (Bubble boy)
  26. 28. Combined immunodeficiencies ( 2 ) 2. Hyper-IgM syndrome 3. Purine nucleoside phosphorylase (PNP) deficiency 4. MHC class Ⅱ deficiency
  27. 29. Clinical features of combined immunodeficiency <ul><li>Onset age at early infants(4 - 5 months) </li></ul><ul><li>Recurrent infection with fungi, virus, bacteria, mycobacterium, protozoa </li></ul><ul><li>Opportunistic infections </li></ul><ul><li>Poor prognosis, early infant deaths </li></ul><ul><li>Severe infection after live virus vaccine and BCG </li></ul><ul><li>GVHD after blood transfusion </li></ul><ul><li>High risk of malignancy </li></ul>
  28. 30. Humoral / B-cell Defects
  29. 31. Predominantly antibody defects ● Panhypogammaglobulinemia X-linked agammaglobulinaemia ( Bruton disease ) Common variable immunodeficiency ( CVID ) Transient hypogammaglobulinaemia of infancy (ITHG) ● Selective Ig deficiency Ig heavy chain deficiency IgA deficiency Selective IgG subclass deficiency
  30. 32. — Bruton disease — mutations in btk — maturation disorder of pre-B cell
  31. 33. CVID—variable ( lack of signals from T cells ) ITHG—delayed maturation of T H function
  32. 34. Predominantly antibody defects Common clinical manifestations: ● Recurrent bacterial infections (sepsis and meningitis) ● Viral ,fungal or protozoan infections rare ● Lymphatic system hypoplasia- tonsils, lymph node ( except CVID ) ● Autoimmune disease
  33. 35. <ul><li>Predominantly antibody defects </li></ul><ul><li>Laboratory test </li></ul><ul><ul><li>● Serum Ig ↓ (< 3 ~ 4g/L ) </li></ul></ul><ul><ul><li>● Natural antibody ↓ ( hemagglutinin titers < 1∶4 ) </li></ul></ul><ul><ul><li>● Common antibody ↓ ,> 2 A , ASO < 1 ∶10 </li></ul></ul><ul><ul><li>● Antibody responses to vaccine antigens ↓ </li></ul></ul><ul><ul><li>● Circulating B cell ( CD 19 + 、 CD 20 +) ↓, </li></ul></ul><ul><li>bearing Ig cell ↓ </li></ul>
  34. 36.                                                                                                .   Cell-Mediated/T cell Immunity
  35. 37. Predominantly T-cell defects 1. CD 4 + deficiency 2. CD 7 + deficiency 3. IL-2 deficiency 4. multiple cytokines deficiency ( IL-2 、 -4 、 -5 ) Not completely understood ??
  36. 38. Destination serum Ig B-cells T-cells genetic defect clinical findings ● Wiskott- IgM↓ Normal Progressive ↓ XL Thrombocytopenia Aldrich Syn Mutation in WAS eczema lymphoma ● Ataxia- IgA, E, G↓ Normal ↓ ATM Ataxia, Telangiectasia IgM ↑ telangiectasia ● DiGeorge Normal or ↓ Normal ↓or normal Deletion of Hypoparathyroidism Syn chromosome conotruncal defect 22q11.2-pter abnormal facies Immunodeficiency syndrome deficiencies
  37. 39. Wiskott-Aldrich Syndrome <ul><li>X-linked Recessive </li></ul><ul><li>Gene defect of WAS protein </li></ul><ul><li>B and T cell dysfunction </li></ul><ul><li>Triad of </li></ul><ul><ul><li>Thrombocytopenia </li></ul></ul><ul><ul><li>Eczema </li></ul></ul><ul><ul><li>Recurrent pyogenic infections </li></ul></ul><ul><li>Treatment – Stem cell or Bone Marrow transplant </li></ul><ul><li>Prognosis - Average life expectancy 11 years </li></ul>
  38. 40. ( eczema )
  39. 41. Ataxia-Telangiectasia <ul><li>Autosomal Recessive </li></ul><ul><li>Have both B and T cell dysfunction </li></ul><ul><ul><li>more characteristics of B cell dysfunction </li></ul></ul><ul><li>Associated Symptoms </li></ul><ul><ul><li>Ataxia from early age – progressive </li></ul></ul><ul><ul><li>Telangiectasia develop after 2 yrs </li></ul></ul><ul><ul><li>High risk for various malignancies </li></ul></ul><ul><ul><li>Endocrine abnormalities – many with Diabetes </li></ul></ul><ul><ul><li>Liver Dysfunction </li></ul></ul><ul><li>Treatment – supportive </li></ul><ul><li>Prognosis – death often in early childhood </li></ul>
  40. 42. Ataxia
  41. 43. telangiectasi a
  42. 44. DiGeorge Syndrome
  43. 45. DiGeorge Syndrome <ul><li>Deletion of chromosome 22q11.2 </li></ul><ul><ul><li>Defective development of 3 rd and 4 th pharyngeal pouches </li></ul></ul><ul><li>Absence of Thymus </li></ul><ul><ul><li>Therefore low or absent T cells </li></ul></ul><ul><ul><li>No B cell abnormalities except in more severe forms. </li></ul></ul><ul><li>Associated Anomalies </li></ul><ul><ul><li>Conotruncal Cardiac Defects </li></ul></ul><ul><ul><ul><li>VSD </li></ul></ul></ul><ul><ul><ul><li>Tetralogy of Fallot </li></ul></ul></ul><ul><ul><ul><li>Interrupted Aortic Arch </li></ul></ul></ul><ul><ul><li>Parathyroid Hypoplasia </li></ul></ul><ul><ul><ul><li>Low Calcium </li></ul></ul></ul><ul><ul><ul><li>Tetany </li></ul></ul></ul>
  44. 46. DiGeorge Syndrome <ul><li>Other Anomalies </li></ul><ul><ul><li>Cleft Palate </li></ul></ul><ul><ul><li>Velocardiofacial Syndrome </li></ul></ul><ul><ul><li>Esophageal abnormalities </li></ul></ul><ul><ul><li>Ocular anomalies </li></ul></ul><ul><ul><li>Renal anomalies </li></ul></ul><ul><ul><li>Increased incidence of Autoimmune disease </li></ul></ul><ul><li>Diagnosis – FISH </li></ul><ul><ul><li>Will often have decreased CD3 T cells </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>IVIG and antibiotic prophylaxis </li></ul></ul><ul><ul><li>Should be on TMP/SFA for PCP prophylaxis </li></ul></ul><ul><ul><li>Thymic transplant or Bone marrow transplant </li></ul></ul>
  45. 47. DiGeorge anormaly
  46. 48. Hypertelorism hooded eyelids short philtrum with fish-mouth appearance , micrognathia Low set ears telecanthus with short palpebral fissures Facial features of children with DiGeorge syndrome
  47. 49. DiGeorge syndrome
  48. 50. Phagocytic Disorders                                                                
  49. 51. Congenital defects of phagocytic number and/or function ● Sever congenital neutropenia ( SCN , Kostmann syndrome ) ● Chronic granulomatous disease ● Chediak-Hiashi syndrome
  50. 52. Bacteria phagosome Bacteria Phagosome Neutrophil NADPH H + NADPH H + e - +O 2 O 2 - H + H 2 O 2 Normsal phagocyte Dysfunction of phagocyte Chronic granulomatous disease
  51. 53. Chronic Granulomatous Disease <ul><li>Rare – 20 cases/year in the US </li></ul><ul><li>Genetics </li></ul><ul><ul><li>70 % X-linked recessive </li></ul></ul><ul><ul><li>Defect in NADPH oxidase </li></ul></ul><ul><ul><li>Can’t form reactive oxygen species to destroy micro-organisms </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Pneumonia, Abscesses, Adenitis, Osteomyelitis </li></ul></ul><ul><ul><li>Uniquely susceptible to Aspergillosis </li></ul></ul>
  52. 54. Chronic Granulomatous Disease <ul><li>Associated Symptoms </li></ul><ul><ul><li>Severe Acne </li></ul></ul><ul><ul><li>Excessive Granulomata – often in GI tract </li></ul></ul><ul><ul><li>Lupus </li></ul></ul><ul><ul><li>Chorioretinitis </li></ul></ul><ul><li>Diagnosis – Nitroblue Tetrazolium Test (NBT) </li></ul><ul><li>Treatment </li></ul><ul><ul><li>Antibacterial and antifungal prophylaxis </li></ul></ul><ul><ul><li>Interferon Gamma </li></ul></ul><ul><ul><li>Stem cell or Bone Marrow Transplant </li></ul></ul>
  53. 55. Complement Disorders
  54. 56. Complement deficiency Defects Inheritance Clinical findings ● Classical pathway Infections , (C1q 、 r 、 s 、 C 2 、 C 4 ) AR Autoimmune disease C 1 inhibitor AD Hereditary angioedema ● Alternaive pathway Recurrent pyogenic infection (C 3 、 FactorⅠ 、 FactorH) AR ● Others Neisseria infection (C 5 ~ 8 、 properdin 、 factor D) AR Lupus-link syndrome C 9 AR Asymptomatic
  55. 57. Common clinical manifestations PID <ul><li>● Infection recurrent </li></ul><ul><ul><li>▼ Age >50 % younger than 3 yrs </li></ul></ul><ul><ul><li>▼ Location respiratory tract , GI tract… </li></ul></ul><ul><ul><li>▼ Pathogen </li></ul></ul><ul><ul><li>▼ Course </li></ul></ul><ul><li>● Malignancy and autoimmune disease </li></ul><ul><li>● Tendency of inheritance <15yrs 80 % male </li></ul><ul><li>● Others </li></ul>
  56. 58. Table 1. Characteristic infections of the primary immunodeficiencies component primary pathogen primary site clinical example T-cells intracellular, bacteria viruses, protozoa, fungi, non-specific SCID, DiGeorge B-cells pneumococcus, streptococcus, haemophilus lung, skin, CNS IgG, IgM deficiency IgG, IgM deficiency enteric bacteria and viruses GI, nasal, eye IgA deficiency phagocytes Staphylococcal, Klebsiella Pseudomonas, lung, skin, regional lymph node Chronic granulomatous disease (CGD) complement neisseria, Haemophilus, pneumococcus, streptococcus CNS lung skin C3, Factors I and H, late C omponents
  57. 59. Approach to the patients with suspected immunodeficiency ● The medical history in immunodeficiency ● Physical examination ● Laboratory investigation
  58. 60. Key History <ul><li>● Get history of infections </li></ul><ul><ul><li>Location </li></ul></ul><ul><ul><li>Organism </li></ul></ul><ul><ul><li>Frequency </li></ul></ul><ul><ul><li>Response to therapy </li></ul></ul><ul><ul><li>Seriousness (i.e. hospitalization) </li></ul></ul><ul><li>● Family History – Including Consanguinity </li></ul><ul><li>● Growth Pattern </li></ul>
  59. 61. From INFO4PI.ORG
  60. 62. Physical finding <ul><li>● Failure to thrive </li></ul><ul><li>● Dysmorphism(abnormal facial features) </li></ul><ul><li>● Skin and mucosa </li></ul><ul><ul><li>Eczema, petechiae </li></ul></ul><ul><ul><li>Abscesses, pyoderma </li></ul></ul><ul><ul><li>Telangiectasia </li></ul></ul><ul><ul><li>Delayed umbilical separation </li></ul></ul><ul><li>● Respiratory tract </li></ul><ul><li>……… </li></ul>
  61. 63. Diagnostic Work Up <ul><li>● Antibody Defects </li></ul><ul><ul><li>Quantitative - Immunoglobulin levels </li></ul></ul><ul><ul><li>Functional - Antibody Titers to immunizations </li></ul></ul><ul><li>● T cell </li></ul><ul><ul><li>Quantitative – CBC, Abs lymphocyte count </li></ul></ul><ul><ul><li>Functional – Skin tests for antigens (Mumps, candida, etc.) </li></ul></ul><ul><ul><li>Chest x-ray </li></ul></ul><ul><li>● Phagocyte </li></ul><ul><ul><li>Quantitative – CBC, Abs neutrophil count </li></ul></ul><ul><ul><li>Functional – NBT test </li></ul></ul><ul><li>● Complement </li></ul><ul><ul><li>Quantitative – C3, C4 </li></ul></ul><ul><ul><li>Functional – CH50 </li></ul></ul>
  62. 64. Initial and advanced laboratory tests for immunodeficiency
  63. 65. From INFO4PI.ORG
  64. 66. Management of PID ● General treatment ● Replacement therapy ● Immune reconstruction ● Gene therapy
  65. 67. General management of PID <ul><li>● Diet </li></ul><ul><li>● Avoidance of pathogens (“germ-free” care) </li></ul><ul><li>● Antibiotics </li></ul><ul><ul><li>Use in acute illness </li></ul></ul><ul><ul><li>Prophylactic </li></ul></ul><ul><li>● Avoid whole blood transfusion in combined immunodeficiency disorder(GVHR) </li></ul><ul><li>● Avoid live virus vaccines and BCG </li></ul>
  66. 68. Bubble Boy
  67. 69. Immunoglobulin replacement <ul><li>Treatment of severe antibody disorders </li></ul><ul><li>● IVIG 400 ~ 600mg/kg/m iv drip </li></ul><ul><li>● Frozen plasma 10ml/kg/month </li></ul><ul><li>◎ Caution with administration of blood production </li></ul><ul><li>if selective IgA deficiency </li></ul>
  68. 70. How to get out of the bubble ?
  69. 71. Specific treatment for cellular deficiency <ul><li>● Bone marrow transplantation </li></ul><ul><li>● Replacement therapy </li></ul><ul><ul><li>Enzyme replacement </li></ul></ul><ul><ul><li>Gene therapy </li></ul></ul><ul><ul><li>Thymic hormones </li></ul></ul><ul><ul><li>Cytokines </li></ul></ul><ul><li>● Fetal thymus transplantation </li></ul>
  70. 72. A new hope for gene therapy of immunodeficency how to get out of the bubble?
  71. 73. Specific treatment of phagocytic disorders ● Interferon gamma for CGD ● Granulocyte transfusion
  72. 74. Case Presentation D. George is a 2 year old male brought in by his parents Wiskott and Aldrich because of concerns about recurrent infections . They state he has been sick many times over the last two years. He has been in the hospital twice with some sort of infection. He has also had frequent upper respiratory infections and has had Otitis Media 7 times in the last two years.
  73. 75. Questions <ul><li>● What other history should we get? </li></ul><ul><li>● Does the child need work up for immunodeficiency? </li></ul><ul><ul><li>Depends on history </li></ul></ul><ul><ul><li>What immunodeficiency should we worry about? </li></ul></ul><ul><ul><li>What work up should be done? </li></ul></ul>
  74. 78. Related website
  75. 79. Thanks you for your attention
  76. 80. Mini case discussion
  77. 81. Case presentation (1) <ul><li>A 3-month -old boy born of non-consanguineous marriage </li></ul><ul><li>presented with recurrent diarrhea and failure to thrive requiring 3 hospitalizations in past. </li></ul><ul><li>born at full term with a birth weight of 3.25 kg and was on exclusive breast feeds. </li></ul><ul><li>received BCG and 1st dose of OPV and DPT. </li></ul><ul><li>had two elder sisters. The eldest of them was small for gestational age, had chronic diarrhea, failure to thrive and died at 2 months of age. The other sister died at 9 months of age due to pneumonia. </li></ul>
  78. 82. Case presentation (2) <ul><li>His weight was 2.7 kg and length was 49 cm. </li></ul><ul><li>He had triangular facies, tonsils were absent and no BCG scar was seen. </li></ul><ul><li>There was no rash, lymphadenopathy or organomegaly. </li></ul>
  79. 83. Case presentation (3) <ul><li>His hemogram showed total leucocyte count of 6,300 cells/cumm with absolute lymphocyte count of 1575 cells/cumm . </li></ul><ul><li>X-ray chest showed no evidence of thymus . </li></ul><ul><li>HIV ELISA was negative. </li></ul>
  80. 84. characteristics <ul><li>3 month old boy </li></ul><ul><li>recurrent infections with failure to thrive </li></ul><ul><li>absent tonsils </li></ul><ul><li>borderline lymphocyte counts </li></ul><ul><li>X-ray chest showed no evidence of thymus </li></ul>
  81. 85. Questions <ul><li>What kinds of diseases did the baby suffer? </li></ul><ul><li>What kinds of Lab tests would you order? </li></ul><ul><li>How can you save his life? </li></ul><ul><li>How about his prognosis? </li></ul>
  82. 86. Diagnosis <ul><li>T-B+ SCID </li></ul>