Fatal outcome in two siblings with Fatal outcome in two siblings with thymic hypoplasia and severe thymic hypoplasia and severe combined immunodeficiencycombined immunodeficiency

Vilnius University Children’s Hospital Pediatric CenterVilnius University Children’s Hospital Pediatric CenterVilnius University Hospital Santariskiu ClinicVilnius University Hospital Santariskiu Clinic

R.R. Duobiene, R.Duobiene, R. MalickaiteMalickaite

First First hhistoryistory

K.M female, born 11.05.K.M female, born 11.05.20200101 Normal delivery after a full term of Normal delivery after a full term of

second pregnancy.second pregnancy. First child unrelated parents.First child unrelated parents. Mother has healthy son from first Mother has healthy son from first

marriage.marriage. Father has healthy daughter from Father has healthy daughter from

first marriage.first marriage.

First historyFirst history

Birth weight 3.1 kg, height 49 cm.Birth weight 3.1 kg, height 49 cm.

Vaccination BCG, HB1, HB2, IPV/DTP without Vaccination BCG, HB1, HB2, IPV/DTP without

complication.complication.

Breast fed till ~3 months. Breast fed till ~3 months.

First Case: history, clinical presentationFirst Case: history, clinical presentation

IV IGIV IGIV IG

Fir

st c

ase

S ym p tom s

C an d id iasis(ora l, n ap k in )

D iarrh ea

F a ilu reto th rive

3 .1 k g 4 .8 k g 5 .1 k g (2 5% ) 4 .2 k g (< 3 % ) 4 ,8 k g

H y p e r in fla te d lu n g sN o th y m ic sh a d ow

B ron ch itis E p iso d e so f d y sp n e a

P n e u m o n ia b ila t .P n e u m o th o ra x d e x .T h or a co c en te s is d e x .

A P V

11 .05 .0 1 3 4 5 6 7 8 9 1 0

1 32 5

5 8 9 1 0 1 2 13 1 4 1 5 16 2 2

6(11 .11 )

7(11 .1 2 )

8(11 .0 1 )

19 20 22 24 26 2 8 3 0 4 18 19 20 21 A ge:d ays

m on th s

B rea s tfe e d in g

D isc h a rg eA d m ittedto U n iv er s ityh o sp ita l

H y p o g am m a g lo b u lin e m ia

O toan tr itis

A n tro m a s to id o to m y

NC ard iovascu lar system

M iop er ic a rd itis (s e c on d a r y )

R esp ira torytract

X R X R

X R

X RX R

C T

B en zy lp e n ici ll in u mG e n ta m y c in u m

C e ftr ia xo n im C e fo ta x im u m F lu ca n a z o lu m

Im ip en em u mF lu ca n a z o lu mM e tro n id az o lu mS tero id sA d ren o m im etic s

Blood countBlood count

UnitsUnits 11dayday 99d.d. 2727d.d. 4747d.d. 5757d.d. 7474d.d.

WBCWBC x10x1099/L/L 8.98.9 7.27.2 10.710.7 9.59.5 15.015.0 11.711.7

LYMLYM x10 x1099/L/L

%%

2.72.7

30.230.2

1.11.1

15.715.7

1.61.6

15.015.0

1.71.7

17.817.8

3.13.1

20.720.7

1.11.1

9.69.6

HGBHGB g/L g/L 119119 108108 9898 9393 112112 117117

MCVMCV fl fl 7171 7272 74.874.8 77.077.0 78.778.7 8282

MCHMCH pg pg 24.624.6 24.124.1 26.126.1 25.825.8 25.125.1 26.826.8

PLT PLT x10x1099/L/L 397397 540540 421421 340340 11001100 329329

EESRSR mm/hmm/h 33 88 77 55 66

CRCRPP mg/Lmg/L <3.7<3.7 <3,7<3,7

ImmunoglobulinsImmunoglobulins

N.V.(6mo)N.V.(6mo) 13.11.200113.11.2001 03.12.03.12.20012001 04.01.04.01.20022002

Ig AIg A g/ g/LL 0.360.36 -- 1.651.65 0.0580.058 0.0560.056 << 0.2250.225

IgG IgG g/ g/LL 3.53.5 -- 11.811.8 << 1.411.41 5.5115.511 3.4353.435

IgM IgM g/ g/LL 0.360.36 -- 1.041.04 n.i.n.i. 0.2370.237 0.5130.513

IgE IgE IU/ml IU/ml << 1515 17.5 17.5

Laboratory findingsLaboratory findings

Additional investigations excluded:Additional investigations excluded: - cyctic fibrosis,- cyctic fibrosis, -- celiac.celiac. ECG, cardioechoscopy don’t revealed ECG, cardioechoscopy don’t revealed

organic patorganic pathhology at first.ology at first. Antrium CTAntrium CT: -: - proc. mastoideus not proc. mastoideus not

aerated, filled with soft tissue density, aerated, filled with soft tissue density, nonhomogeneus content.nonhomogeneus content.

Abdominal USS Abdominal USS -- normal. normal. Chest XRChest XR:: -- hyperinflated lungs, hyperinflated lungs,

- - no thymic shadow no thymic shadow..

Right pneumothorax

Laboratory findingsLaboratory findings

Stool cultureStool culture:: – – Citrobacter, Morganella morganii, Citrobacter, Morganella morganii, L(-) E.coli, KlebsiellaL(-) E.coli, Klebsiella Swab from the tongue, esophagus - Swab from the tongue, esophagus - Candida sp.Candida sp. Urine culture – Urine culture – S.saprophyticusS.saprophyticus Culture from intubation tube –Culture from intubation tube – Enterococcus faecalis, Enterococcus faecalis,

S.epidermidis.S.epidermidis. Antrial culture –Antrial culture – negativenegative Blood culture –Blood culture – negativenegative Stool culture for Stool culture for Campylobacter sp.Campylobacter sp. – negative – negative Latex test for rotaviruses - negativeLatex test for rotaviruses - negative

Patanatomical findingsPatanatomical findings

Hassall’s corpuscles

Lymphocytes

The thymus shows disorganized epithelial cells with very few lymphocytes and no Hassall’s corpuscles

Second HistorySecond History

B.M. female, born 21.10.B.M. female, born 21.10.20200202

Normal pregnancy and deliveryNormal pregnancy and delivery

Birth weight 3.4 kgBirth weight 3.4 kg

Vaccination BCG, HB1, HB2, IPV/DTPVaccination BCG, HB1, HB2, IPV/DTP without any complicationwithout any complicationss

Only breast feedingOnly breast feeding

B loo d co m p o n en tstran sfu sion s

S k in rash es

D iarrh ea

P n eu m o n ia

B r o n c h it is

Seco

nd

case

s

S ym p to m s

R h in itis

S u b fe b r ile( te m p e r a tu re )

U rin a ryin fec tion

S e ro o t it isC o n ju n c tiv it is

H ep ato m ega ly

C a rd iov ascu lar system

S e izu res

1 . P neum onia sin .2 . P neum onia dex .3 . P leur itis dex4 . T horacocentesis d ex5 . H aem othorax in susp .

1 . E . C oli2 . C andida sp .

1 . C andida sp .2 . C lostr id ium d ifficile3 . E nterobacter

A dm itted toreg . hosp ita l

2 6 2 7 2 8 2 9 1 2 3 4 5 6 7 8 9 1 0 11 1 2 1 3 1 4 1 5 1 6 17 1 8 1 9 2 0

31 2 5

2 2 2 4 25 3 1 1 5 7 8 9 1 0 11 1 2 1 3 1 4 1 5 1 7 1 8 9 2 0

6(2 1 .0 4 )

2 2 2 3 24 2 5 2 6 A g e:

daysm on th sTo U n iversity

hosp ita l

C M V IgG (-)

O p e n fo r a m e n o v a leS e c o n d a r y m io c a r d ic le s io n s

P C R C M V (+ )

12

3 45

1

IV IG

2 1 .1 0 .0 2

IV IG

X R X RX R

H y p o g a m m a g lo b u lin e m ia

2 1 .0 2 .0 3 (2 1 .0 3 )

Second case: hSecond case: historyistory, clinical presentation, clinical presentation

Blood countBlood count

03.0303.03..0303 19.0319.03 01.0401.04 14.0414.04 25.0425.04

WBCWBC x10x1099/L/L 33.6.6 2.52.5 2.52.5 2.92.9 0.80.8

LYMLYM x10 x1099/L/L

%%

1.51.5

42.042.0

1.51.5

58.858.8

1.11.1

43.643.6

1.81.8

64.064.0

0.60.6

80.380.3

HGBHGB g/L g/L 9191 104104 139139 113113 9696

MCV MCV flfl 76.976.9 7575.0.0 8181.0.0 74.874.8 8181.0.0

MCHMCH pgpg 25.625.6 24.624.6 26.626.6 26.826.8 28.028.0

PLTPLT x10 x1099/L/L 127127 117117 6060 2020 1616

EESRSR mm/hmm/h 55 33 44 22 2929

ImmunoglobulinsImmunoglobulins

N. V.N. V. 19.19.03.0303.03 08.04.0308.04.03 1414.04..04.0303

IgAIgA g/l g/l 0.360.36 -- 1.651.65 0.240.24 << 0.230.23 0.240.24

IgG IgG g/l g/l 3.53.5 -- 11.811.8 1.351.35 3.03.000 12.0512.05

IgMIgM g/l g/l 0.360.36 -- 1.041.04 0.280.28 << 0.170.17 0.20.277

IgE IgE IU/mlIU/ml << 1515.0.0 << 19.119.1 << 19.119.1

Lymphocytes populations: T-, B+, NK+Lymphocytes populations: T-, B+, NK+

ParameterParameter ValueValue Normal valueNormal value

Absolute lymphocytesAbsolute lymphocytes countcount 2626 % / 1508 mm % / 1508 mm33 39 – 59 % / 2700-5400 mm39 – 59 % / 2700-5400 mm33

CD3+CD3+ 1 % / 15 mm1 % / 15 mm33 58 - 67 % / 1700 – 3600 mm58 - 67 % / 1700 – 3600 mm33

CD3+CD4+CD3+CD4+ 0 %0 % 38 – 50 % / 1700 – 2800 mm38 – 50 % / 1700 – 2800 mm33

CD3+CD8+CD3+CD8+ 0 %0 % 18 – 25 % / 800 - 1200 mm18 – 25 % / 800 - 1200 mm33

CD16+/CD56+CD16+/CD56+ 9 % / 136 mm9 % / 136 mm33 8 – 17 % / 300 – 700 mm8 – 17 % / 300 – 700 mm33

CD19+CD19+ 91 % / 1372 mm91 % / 1372 mm33 19 - 31 % / 500 – 1500 mm19 - 31 % / 500 – 1500 mm33

Lymphocytes transformation Lymphocytes transformation test against PHAtest against PHA

2%2% 30 – 40 %30 – 40 %

Lymphocytes transformation Lymphocytes transformation test against PWMtest against PWM

4%4% 8 –10 %8 –10 %

Neutrophyl rNeutrophyl respiratory burstespiratory burst spontaneous / PMA stimulationspontaneous / PMA stimulation

8 8 %% / / 70%70% 15 - 25 15 - 25 %% / / 45 – 65 %45 – 65 %

Laboratory findingsLaboratory findings

Anti tAnti tooxo IgM (-)xo IgM (-), IgG (-/+), IgG (-/+) Anti EBV IgM (-), IgG (-)Anti EBV IgM (-), IgG (-) IFA rIFA r.. forfor HHIV 1/2IV 1/2 0 0 (-) (-)

Anti rubella IgM (-)Anti rubella IgM (-), , IgGIgG (+)(+) Anti HBsAnti HBs (+)(+) ( (20.20.03)03)

Anti CMV IgG (-) Anti CMV IgG (-) ((20.20.03)03) CMV PCR positive (CMV PCR positive (25.25.04)04)

Laboratory findingsLaboratory findings

Urine culture – Urine culture – E.coli, Candida spp.E.coli, Candida spp.

Faeces test, culture – Faeces test, culture – Clostridium difficile, Clostridium difficile, Enterobacter, Enterobacter, Candida spp.Candida spp.

Haemoculture – Haemoculture – Enterobacter sp., Enterobacter sp., Pseudomonas aeruginosa. Pseudomonas aeruginosa.

Culture from pleural fluid – negative.Culture from pleural fluid – negative.

Further investigationsFurther investigations

Chest CChest CT:T:

Thymus size – Thymus size – 13.6 x 19.6 x 11.1 mm13.6 x 19.6 x 11.1 mm. Thymus . Thymus lower part was compounded olower part was compounded off adipose adipose tissue.tissue.

CardiologistCardiologist: : opened foramen ovale, no other opened foramen ovale, no other

organic patorganic pathhology.ology. Chest XR: hyperinflated lungs,Chest XR: hyperinflated lungs, no thymic shadowno thymic shadow..

Pneumonia with right pleuritis

Haemothorax

TreatmentTreatment

GentamGentamiicincinumum CetriaxonumCetriaxonum BenzylpenicillinumBenzylpenicillinum Co-trimoxazolumCo-trimoxazolum CefotaximumCefotaximum AmoAmoxicillinum et ac.clavul.xicillinum et ac.clavul. Imipenemum et cilastinumImipenemum et cilastinum SultamicillinumSultamicillinum

IntrIntracaconazolonazolumum FluFluccanazolanazolumum

MetronidazolumMetronidazolum

AciclovirumAciclovirum ValaciclovirumValaciclovirum

MetMethyhylprednisolonlprednisolonumum CiclosporinumCiclosporinum

EndobulinEndobulinumum x 3 x 3

Not irradiated blood Not irradiated blood componentscomponents transfusions transfusions::

EM x 3EM x 3 PPM x 1M x 1 Plasma Plasma x 5x 5

ConclusionsConclusions

Severe Severe immunodeficiencyimmunodeficiency– fatal by age – fatal by age 1 year.1 year.

T-T- B+NK+ SCID.B+NK+ SCID. Suspected IL-7 RSuspected IL-7 Rchain deficiency.chain deficiency. Fatal outcome (II) – uncontroled CMV.Fatal outcome (II) – uncontroled CMV. Parents Parents could be could be geneticgeneticallyally testedtested. .

Thanks for your attentionThanks for your attention