"The Case of baby J.K" by Areen.A.E Mittib

Severe combined immunodeficiency

(SCID): Omenn syndrome

Done by:

Areen Mittib

"The Case of baby J.K" by Areen.A.E Mittib

Severe combined immunodeficiency (Omenn syndrome): case Report By Areen.A.E Mittib Immunology course Al-najah university-faculty of medicine

Summary: The case involves an infant who suffers from recurrent infection. He was diagnosed with severe combined immunodeficiency (SCID) which is a type of genetic disorder represented by T cell deficiency as well as B cell defi-ciency. SCID results from an aberration in the development of different classes of immune cells receptors due to a defect in the molecular mechanism known as somatic recombination which RAG enzymes play a critical role in it. This patient had suffered from bladder infection, recurrent ear infection as-sociated with chronic diarrhea and failure to thrive. Early recognition of SCID is a pediatric emergency and awareness of this condition should lead to a more sympathetic management of the case.

Introduction: SCID (bubble boy disease) is a genetic disease that results when one of the thirteen genes involved in a molecular mechanism known as somatic re-combination is mutated. Somatic recombination is responsible for giving rise to variable B and T cell receptors. It's classified to many types accord-ing to the mutated gene. Omenn syndrome is the type results when RAG coding gene is mutated (1) (4).

It’s relatively uncommon with a prevalence of approximately 1 in 100,000 births. Babies with SCID, if untreated, usually die within 1 year unless they have undergone successful Hematopoietic stem cell transplantation or oth-er treatments (1) (4).

Its clinical features are severe microbial infections early in life and often as-sociated with chronic diarrhea and failure to thrive (1) (4).

"The Case of baby J.K" by Areen.A.E Mittib

Case History:

At birth, Baby J.K was a normal baby boy. Both of his parents were in

their late twenties and were healthy. At the fourth weak, J.K developed a middle-ear infection .He suffered from recurrent ear infections over the next three months, which required antibiotic treatment (3). His pediatrician recommended taking of the fluid from his ear and Cultures of the drainage fluid showed the presence of Homophiles influenza (3). At the third months of age, J.K had four episodes of diarrhea which persisted for 3–5 days each time. J.K also was not gaining weight as rapidly as was expected during this time. At the fourth months, he developed another ear in-fection, this one more severe than the first. His mother mentioned unusual ,unpleasant odor when she changes his diapers .Ear’s fluid specimen was taken and cultured , the culture revealed the presence of Pseudomonas aeruginosa and his doctor determined that J.K suffered from bladder infec-tion (3). No lymph nodes could be palpated in J.K’s neck or axilla. His heart, lungs, liver, and spleen were of normal size (3).

Diagnosis: His physicians took a blood sample for a complete blood count (CBC). The results show normal RBC and platelet number but low WBC number espe-cially T cell and B cell while high number of NK .A sample of J.K’s DNA was sent for sequence analysis, which revealed mutations in both copies of his RAG gene (3)(4)(1)

Discussion: J.K suffered from recurrent ear infection, the first was at age four weeks by haemophilus influenza and the second was at age four months by Pseu-domonas aeruginosa , urine odor indicate that there was bladder infection . All these infections indicate there is no response by Adaptive immune sys-tem for bacterial infection (immunodeficiency). Complete blood count (CBC) shows normal RBC and platelet number but low WBC number especially T cell and B cell while high number of NK. B and T cell failed to mature and undergo apoptosis (negative selection) so their numbers are low.

"The Case of baby J.K" by Areen.A.E Mittib

J.Ks condition diagnosed as severe combined immunodeficiency omenn type and was confirmed by DNA sequence analysis, which revealed mutations in both copies of his RAG gene. The mutations in both genes which resulted in a complete lack of expression of functional RAG protein.

Conclusion: This Case about infant who suffers from recurrent infection and diagnosed with severe combined immunodeficiency (SCID) which is a type of genetic disorder represented by T cell deficiency as well as B cell deficiency. Omenn syndrome forms due to genetic mutation in gene responsible for expression of RAG enzymes .RAG enzymes play a critical role in develop-ment of T and B receptors by process known as somatic recombination. complete loss of these enzymes cause inability of T cell and B cell to ma-ture and then by negative selection these cell will die , so the number of these lymphocyte will decrease.

Treatment: J.K was received intravenous antibiotics to treat the ear and bladder infec-tions and intravenous fluids. He recovered from the infections but remained weak.

My own opinion: NK number in CBC was high. Its number increases as an alternative of T and B cell because of no somatic recombination mechanism needed for its receptor formation.

"The Case of baby J.K" by Areen.A.E Mittib

I think about Gene therapy or bone marrow transplantation for long term treatment .But may transplant bone marrow rejects by the large number of NK.

Appendices:

References: 1-Santagata S, Villa A, Sobacchi C, Cortes P, Vezzoni P (2000). "The genet-ic and biochemical basis of Omenn syndrome". Immunology Rev. 178: 64-74 2- : Parham, Peter. 2005. The Immune System, 2nd Edition. Garland Sci-ence, New York, NY. 3- Munoz-Robles, J., M.J. Del Rey, J. Ruiz-Contreras, et al.. Partial Im-mune Reconstitution after Bone Marrow Transplantation in a Boy with Recombination Activating Gene 1 Defect. Bone Marrow Transplantation 33(8):877–878 4- Villa, A., C. Sobacchi, L.D. Notaraneglo, et al. V(D)J Recombination De-

fects in Lymphocytes due to rag Mutations: Severe Immunodeficiency with a Spectrum of Clinical Presentations. Blood 97(1):81–88.