1. Fatal outcome in two siblings with thymic hypoplasia and severe combined immunodeficiency Vilnius University Children’s Hospital Pediatric Center Vilnius University Hospital Santariskiu Clinic R. Duobiene, R. Malickaite

2. First history  K.M female, born 11.05.2001  Normal delivery after a full term of second pregnancy.  First child unrelated parents.  Mother has healthy son from first marriage.  Father has healthy daughter from first marriage.

3. First history  Birth weight 3.1 kg, height 49 cm.  Vaccination BCG, HB1, HB2, IPV/DTP without complication.  Breast fed till ~3 months.

4. First Case: history, clinical presentation

5. Blood count Units Units 1day 1day 9d. 27d. 47d. 57d. 74d. WBC x10 9 /L 8.97.210.79.515.011.7 LYM x10 9 /L % %2.730.21.115.71.615.01.717.83.120.71.19.6 HGB g/L 1191089893112117 MCV fl 717274.877.078.782 MCH pg 24.624.126.125.825.126.8 PLT x10 9 /L 3975404213401100329 ESR mm/h 38756 CRP mg/L <3.7<3,7

6. Immunoglobulins N.V.(6mo)13.11.2001 03.12.2001 04.01.2002 Ig A g/L 0.36 - 1.65 0.0580.056 < 0.225 IgG g/L 3.5 - 11.8 < 1.41 5.5113.435 IgM g/L 0.36 - 1.04 n.i.0.2370.513 IgE IU/ml < 15 17.5

7. Laboratory findings  Additional investigations excluded: - cyctic fibrosis, - cyctic fibrosis, - celiac. - celiac.  ECG, cardioechoscopy don’t revealed organic pathology at first.  Antrium CT: - proc. mastoideus not aerated, filled with soft tissue density, nonhomogeneus content.  Abdominal USS - normal.  Chest XR: - hyperinflated lungs, - no thymic shadow.

8. Right pneumothorax

9. Laboratory findings  Stool culture: – Citrobacter, Morganella morganii, L(-) E.coli, Klebsiella L(-) E.coli, Klebsiella  Swab from the tongue, esophagus - Candida sp.  Urine culture – S.saprophyticus  Culture from intubation tube – Enterococcus faecalis, S.epidermidis.  Antrial culture – negative  Blood culture – negative  Stool culture for Campylobacter sp. – negative  Latex test for rotaviruses - negative

10. Patanatomical findings Hassall’s corpuscles Lymphocytes The thymus shows disorganized epithelial cells with very few lymphocytes and no Hassall’s corpuscles

11. Second History  B.M. female, born 21.10.2002  Normal pregnancy and delivery  Birth weight 3.4 kg  Vaccination BCG, HB1, HB2, IPV/DTP without any complications without any complications  Only breast feeding

12. Second case: history, clinical presentation

13. Blood count 03.03.03 19.0301.0414.0425.04 WBC x10 9 /L 3.6 3.62.52.52.90.8 LYM x10 9 /L % % 1.5 1.542.01.558.81.143.61.864.00.680.3 HGB g/L 9110413911396 MCV fl 76.9 75.0 81.0 74.8 MCH pg 25.624.626.626.828.0 PLT x10 9 /L 127117602016 ESR mm/h 534229

14. Immunoglobulins N. V. 19.03.03 08.04.03 14.04.03 IgA g/l 0.36 - 1.65 0.24 < 0.23 0.24 IgG g/l 3.5 - 11.8 1.35 3.00 12.05 IgM g/l 0.36 - 1.04 0.28 < 0.17 0.27 IgE IU/ml < 15.0 < 19.1

15. Lymphocytes populations: T-, B+, NK+ ParameterValue Normal value Absolute lymphocytes count 26 % / 1508 mm 3 39 – 59 % / 2700-5400 mm 3 CD3+ 1 % / 15 mm 3 58 - 67 % / 1700 – 3600 mm 3 CD3+CD4+ 0 % 38 – 50 % / 1700 – 2800 mm 3 CD3+CD8+ 0 % 18 – 25 % / 800 - 1200 mm 3 CD16+/CD56+ 9 % / 136 mm 3 8 – 17 % / 300 – 700 mm 3 CD19+ 91 % / 1372 mm 3 19 - 31 % / 500 – 1500 mm 3 Lymphocytes transformation test against PHA 2% 30 – 40 % Lymphocytes transformation test against PWM 4% 8 –10 % Neutrophyl respiratory burst spontaneous / PMA stimulation 8 % / 70% 15 - 25 % / 45 – 65 %

16. Laboratory findings  Anti toxo IgM (-), IgG (-/+)  Anti EBV IgM (-), IgG (-)  IFA r. for HIV 1/2 0 (-)  Anti rubella IgM (-), IgG (+)  Anti HBs (+) (20.03)  Anti CMV IgG (-) (20.03)  CMV PCR positive (25.04)

17. Laboratory findings  Urine culture – E.coli, Candida spp.  Faeces test, culture – Clostridium difficile, Enterobacter, Enterobacter, Candida spp. Candida spp.  Haemoculture – Enterobacter sp., Pseudomonas aeruginosa.  Culture from pleural fluid – negative.

18. Further investigations  Chest CT: Thymus size – 13.6 x 19.6 x 11.1 mm. Thymus lower part was compounded of adipose tissue. Thymus size – 13.6 x 19.6 x 11.1 mm. Thymus lower part was compounded of adipose tissue.  Cardiologist: opened foramen ovale, no other organic pathology.  Chest XR: hyperinflated lungs, no thymic shadow. no thymic shadow.

19. Pneumonia with right pleuritis

20. Haemothorax

21. Treatment  Gentamicinum Cetriaxonum Cetriaxonum Benzylpenicillinum Benzylpenicillinum Co-trimoxazolum Co-trimoxazolum Cefotaximum Cefotaximum Amoxicillinum et ac.clavul. Amoxicillinum et ac.clavul. Imipenemum et cilastinum Imipenemum et cilastinum Sultamicillinum Sultamicillinum  Intraconazolum Flucanazolum Flucanazolum  Metronidazolum  Aciclovirum  Valaciclovirum  Methylprednisolonum  Ciclosporinum  Endobulinum x 3  Not irradiated blood components transfusions: EM x 3 EM x 3 PM x 1 PM x 1 Plasma x 5 Plasma x 5

22. Conclusions  Severe immunodeficiency– fatal by age 1 year.  T- B+NK+ SCID.  Suspected IL-7 R  chain deficiency.  Fatal outcome (II) – uncontroled CMV.  Parents could be genetically tested.

23. Thanks for your attention