A 3-month-old girl was referred for recurrent fever, pneumonia, diarrhea, chronic dermatitis, failure to thrive, and motor retardation. The patient was the daughter of consanguineous parents and had a female sibling who had died due to recurrent infections. She suffered from oral thrush and a diffuse brownish colored macular rash on the trunk. Chest auscultation revealed bilateral crackles at the lower zones. Chest X-ray, indicated the absence of thymus shadow; a para-cardiac infiltration and an inferolateral squaring scapulae were demonstrated.Laboratory tests revealed mild anemia with profound lymphocytopenia, and hypogammaglobulinemia. adenosine deaminase (ADA) enzyme activities were low.What is the diagnosis?
Based on the above clinical scenerio,the diagnosis is Severe combined immunodeficiency. Severe combined immunodeficiency (SCID), is a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes Types of SCID X-linked severe combined immunodeficiency Purine nucleoside phosphorylase deficiency Adenosine deaminase deficiency Omenn syndrome Bare lymphocyte syndrome JAK3 Aemis/DCLRE1C X-linked severe combined immunodeficiency Most cases of SCID are due to mutations in the gene encoding the common gamma chain (gc), a protein that is shared by the receptors for interleukins These interleukins and their receptors are involved in the development and differentiation of T and B cells. The common gamma chain is encoded by the gene IL-2 receptor gamma, or IL-2Rg, which is located on the X-chromosome. For this reason, immunodeficiency caused by mutations in IL-2Rg is known as X-linked severe combined immunodeficiency. The condition is inherited in an X-linked recessive pattern. Adenosine deaminase deficiency: The second most common form of SCID after X-SCID is caused by a defective enzyme, adenosine deaminase (ADA), necessary for the breakdown of purines. Lack of ADA causes accumulation of dATP. The effectiveness of the immune system depends upon lymphocyte proliferation and hence dNTP synthesis. Without functional ribonucleotide reductase, lymphocyte proliferation is inhibited and the immune system is compromised. Purine nucleoside phosphorylase deficiency An autosomal recessive disorder involving mutations of the purine nucleoside phosphorylase (PNP) gene. PNP is a key enzyme in the purine salvage pathway. Impairment of this enzyme causes elevated dGTP levels resulting in T-cell toxicity and deficiency. Symptoms and diagnosis of SCID: Children with SCID are at risk for life-threatening infections. From their first months of life, they have infections that may be frequent, severe, long-lasting or hard to treat. Infections may occur in the lungs (pneumonia), around the brain and spinal cord (meningitis) or in the blood stream. The delay in detection is because newborns carry their mothers antibodies for the first few weeks of life and SCID babies look normal. treatment for SCID: bone marrow transplantation, Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID gene therapy Reference: Harpers illustrated biochemistry 30th edition
Gout
Dwarfism
Mental retardation
Immunodeficiency
Metabolism of protein and amino acid