A CASE REPORT OF A 4 MONTH OLD BOY WITH SEVERE COMBINED IMMUNODEFICIENCY DISORDER Mutua C, Karimi. D, Irungu. A, Patil. R, Ngwatu. P, Manguyu W Kiptum D Gertrude’s Children Hospital Nairobi, Kenya

Outline Background Methods Case presentation Discussion Conclusion References

Background 4 month old boy Diarrhoea and vomiting for 1 week Difficulty in breathing, poor breastfeeding for one day. Treated severally as an outpatient for reflux, Rotaviral GE and Eczema Rotavirus vaccine was given Second and only child in the family First born sibling died at age 4 months with pneumonia

Haemogram RBC-MICROCYTIC HYPOCHROMIC CELLS. WBC-MILD LYMPHOPENIA,NO ATYPICAL CELLS SEEN PLATELETS-ADEQUATE

Management Antimicrobials Respiratory support Intravenous immunoglobulins Psychoeducation to the family Isolation for barrier nursing Advised on a bone marrow transplant

Progress after diagnosis Admitted thereafter for 6 times With sepsis, rotavirus GE For monthly IVIG Succumbed at 11 months

SCID (Severe combined immunodeficiency ) Life-threatening syndrome Recurrent infections, diarrhoea, dermatitis, failure to thrive. Caused by numerous molecular defects leading to compromise in the number and function of T cells B cells, natural killer (NK) cells.

Epidemiology The incidence reported at approximately 1 in 50,000 Average age at symptom onset, 2 months; mean age at diagnosis, 6.5 months The overall male-to-female ratio is 3:1 No racial predisposition exists

Pathophysiology Results from mutations in any of more than 15 known genes Molecular defects block the differentiation and proliferation of T cells and B cells and NK cells. Antibody production is impaired because of the lack of T-cell help Loss of immunity results in opportunistic infections

Genetic defects Mutation of the common γ chain of the interleukin (IL) Autosomal recessive SCID includes the following deficiencies: Janus-associated kinase 3 (JAK3) deficiency Adenosine deaminase (ADA) deficiency

Diagnosis Complete blood count, serum immunoglobulin levels Lymphocyte markers (differentiate forms of SCID) Lymphocyte function assessment Molecular studies to identify genetic defects Autopsy: thymus, peripheral lymphoid tissues Chest radiograph: thymus, pneumonia Prenatal diagnosis, Newborn screening test

Management Pharmacologic prophylaxis against infection IVIG replacement therapy Haematopoetic bone marrow transplantation(HBMT) Enzyme replacement Gene Therapy

Management.. Isolation, strict infection prevention Irradiated and lymphocyte deplete blood transfusions Empiric broad spectrum antimicrobials Avoid live vaccines

Conclusion SCID is a pediatric emergency HBMT is the primary treatment of choice Patients treated with HBMT before age 3.5 months have better survival 97% vs 77%. High index of suspicion key to early diagnosis

References Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010 Feb. 125(2 Suppl 2):S182-94. Erman B, Bilic I, Hirschmugl T, Salzer E, Boztug H, Sanal Ö, et al. Investigation of genetic defects in severe combined immunodeficiency patients from Turkey by targeted sequencing. Scand J Immunol. 2017 Jan 21. Liao CY, Yu HW, Cheng CN, Chen JS, Lin CW, Chen PC, et al. A novel pathogenic mutation on Interleukin-7 receptor leading to severe combined immunodeficiency identified with newborn screening and whole exome sequencing. J Microbiol Immunol Infect. 2018 Mar 2. Railey MD, Lokhnygina Y, Buckley RH. Long-term clinical outcome of patients with severe combined immunodeficiency who received related donor bone marrow transplants without pretransplant chemotherapy or post-transplant GVHD prophylaxis. J Pediatr. 2009 Dec. 155(6):834-840.e1.

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