CASE CONFERENCE

Álvaro Coronado

3m & 18d infant: Poor weight gain Vomits

2mo no more than 2 ounces. More than 2 ounces: vomites, nb/nb, non

projectile He went to PMD who prescribed

Domperidone 3 mo pediatric GI Breastfeeding +

Pantoprazole. Stop Domperidone.

1week later no weight gain, change to Nutramigen.

2 weeks later in GI FU they notice no weight gain patient has liquid stools nb/nm 4 bm/day since 5 days ago and mild to moderate dehydration, patient admitted.

ROS

Cough since he was 2wo. More frequent during the nights and with feedings.

Liquid stools have been coming and going since he was born, parents thought it was normal, related to BF and formula.

PMH

Birth 38w NSVD. No problems during pregnancy

or delivery. W 3430gr. Mom 30yo, G1 Newborn screening: negative (PKU, TSH,

17OH progesterone, total galactose, galactose 1P)

Newborn jaundice, maximum TB level at 3rd day was 12mg/dl

PMH

2 wo: 1 episode of apnea 1 mo: Patent Foramen ovale 2 mo: RSV No admissions, no surgeries Vaccins: BCG at birth. DTaP, HiB, Hep B,

Rotavirus & PCV at 2mo

FMH

Mom 30yo Asthma Father 33yo thyroid nodule, no

treatment.

PE

Length: 58cm Weight: 3,830gr T:37.2/98.96 HR:142x´ RR:56x’ SatO2:

88% Fussy, poor activity

..

.

Skin: red, enlarged blood vessels in forehead, left side.

HEENT: Sunken eyes, PERRL; Ears, TM non erythematous; oral mucosa dry, no tonsils, pharynx non erythematous; Facial asymmetry? More volume in left side.

Neck: no masses, head tilt to the right side but can be moved to both sides on examination.

Heart: RRR, nl S1S2, no murmurs, no rubs Lungs: costal retractions. Symmetric air

passage. No wheezing, no crackles. Abd: BS+, NT/ND, no HSM GU: undescended testis can be palpated

in the inguinal canal, circumcised . Neuro: hypotonic, Root+, Suction+,

Moro+. No head control, no smiles.

Assessment

FTT Vomits: r/o Hypertrophic pyloric stenosis

vs malrotation r/o congenital disease r/o tracheoesophagial fistula

Orders:

Abdominal US Upper GI tract xray gastric emptying gammagraphy PRN US

and GI xray results Chest xray UA, VBG, CBC, BMP IV D5 / PO trial w/formula maximum 2 oz

q3hrs / Esomeprazole

Abdominal US

No Hypertrophic Pyloric Stenosis

Labs 26/10

HemOnc consult

Labs (26/10)

Labs 26/10

Labs 26/10

Chest xray 26/10

Upper GI study 27/10

HemOnc

Peripheral smear: No lymphocytes High monocytes & Eos to compensate

the lack of Lymphocytes.

A: R/O immunologic disease P: Consult Immunology

Orders:

TORCH: Negative HIV: Negative Lymphocytes B & T CD3, CD4, CD8, CD19, CD20, CD11 Serum IgA, IgG IgM

Labs

Normal Values Igs 3mo

IgG 334IgA 17IgM 49

Immunology consult Chest x ray: no thymus Assessment:

SCID vs CID Plan:

Wait for lymphocytes counts Isolation R/o occult infection: CT head to pelvis Consult pulmonary with CT Continue PO per Feeding tube, try to give breast

milk Cultures blood, urine & stool ATB: Cefepime 200mg EV c/12h Vancomycin 40mg

EV c/6h

Cráneo

Cara - cuello

Tórax

Pulmonary consult

Assessment: Chronic aspiration syndrome: r/o

pneumonia r/o TEF

Plan: Continue with Feeding tube Continue with ATB Bronchoscopy & BAL if needed for culture.

Labs results

Normal values 3-6 mo:CD4 1.8-4CD8 0.59-1.6CD3 2.5-5.6CD19 0- 84%CD56 5 -29%

FU – Immunology

SCID ADA deficiency vs X- linked

Plan: Bone marrow transplant ADA, IL2 & IL2 receptor Add antiviral & antimycotic

Day-3

Fever: 38°C/101 PE: crackles in right baseRest of PE unremarkable ADA: 9.7

Peds team plan & orders

Bone marrow transplant: USA Treatment and prophylaxis

Cefepime Vancomycin TMP/SMX INH Acyclovir IVIG infused and monitored by critical care

team Consult Peds ID

Consult ID

Mild infectious process, doesn´t seem to be an aggressive germ

Repeat Cultures Urine x 2 (-) Stools (-) Blood x 2 (-)

Discontinue Vancomycin and acyclovir r/o Disseminated BCG infection

Day 5 Patient transferred to Jackson Memorial – Holtz Children´s Hospital, Miami, Fl

SCID – ADA deficiency confirmed

SEVERE COMBINED IMMUNE DEFICIENCY

Most severe immunodeficiency Lack of adaptative immune function:

absence of NK 1 defective gene of 13 that encodes the

immune system of lymphoid cell.

Pathogenesis

Patients with SCID have very small thymuses with no thymocytes

Spleen depleted of lymphocytes Lymph nodes, tonsils, adenoid and Peyer

patches are absent or extremely underdeveloped.

Present within the 1st few months of life with recurrent or persistent diarrhea, pneumonia, otitis media, sepsis, and cutaneous infections

Clinical manifestations Most of the patients can't gain weight because

of the infections and diarrheas. FTT. Exposed to opportunistic infections (CMV,

Pneumocystis, Candida, RSV, Rotavirus vaccine infection, MMR-v and BCG)

High risk of severe or fatal graft versus host disease (GVHD) from T lymphocytes in non irradiated blood products or in allogeneic stem cell transplants or less severe GVHD from maternal immunocompetent T cells that crossed the placenta while the infant was in uterus.

Diagnosis

Flow cytometry All molecular types of SCID lack T-cells

the lymphocyte count is <2500/mm3 Patients with ADA deficiency have the

lowest count <500/mm3 Immunoglobulines low or absents

Classification of SCID

X-linked: Most common type, 47% of SCID cases in

the US. T – NK – B +Autosommal Recessive: 12 forms, most

common ADA deficiency: 15% of the patients. It can present with

mild cases Bone abnormalities: Chondro-osseous

dysplasia

Number of T cell receptor excision circles (TRECs) from dried blood spots on newborn screening cards using PCR

The number of TRECs is used to assess the number of T cells emigrating from the thymus gland, and therefore is a correlate of thymic function

SCID patient has around 30 circles, normal patient around 1000 circles, in NY the cut is set at 200 cicles

Newborn screening

Differential Dx. Extreme malnutrition Intestinal lymphangiectasia with profound

lymphopenia and hypogammaglobulinemia Hereditary folate malabsorption X-linked hyper-IgM syndrome Wiskott-Aldrich syndrome Calcium channel deficiencies complete DiGeorge syndrome

In younger than 3mo >94% of cases can be treated successfully with HLA-identical or T-cell–depleted haploidentical (half-matched) parental hematopoietic stem cell transplantation without the need for pretransplant chemoablation or post-transplant GVHD prophylaxis.

ADA-deficient SCID and X-linked SCID have been treated with somatic gene therapy; although serious adverse events occurred in the case of X-SCID.

ADA-deficient SCID is also managed with repeated injections of polyethylene glycol modified bovine adenosine deaminase (PEG-ADA).

Treatment

Adkinson: Middleton's Allergy: Principles and Practice, 7th ed.; Chapter 46

Nelson Textbook of Pediatrics, 19th ed.; Chapter 125

New insights into the pathogenesis of adenosine deaminase-severe combined immunodeficiency and progress in gene therapy. - Sauer AV - Curr Opin Allergy Clin Immunol - 01-DEC-2009; 9(6): 496-502

Systematic Evidence Review of Newborn Screening and Treatment of Severe Combined Immunodeficiency. Pediatrics – Vol 125 N 5, Mayo 2010.

UptoDate: SCID an overview & ADA deficiency Department of health, State of NY Adeli MM, Buckley RH: Why newborn screening for

severe combined immunodeficiency is essential: A case report. Pediatrics 2010; 126(2):e465-e469.

Bibliografia