Dr Ira Shah
MD, DCH (Gold Medalist), FCPS, DNB

A seven months old male infant born of non-consanguineous marriage presented with recurrent oral ulcers, fever along with failure to thrive since 4 months. He had macular rash over face and chest since 1 month. He had been hospitalized for pneumonia 15 days back. He was a full term normal vaginal delivery and birth weight was 3.1 kg. His elder 2 sisters were completely asymptomatic. He had been immunized till date and milestones were normal. On examination, he had pallor with hypo-pigmented macules over neck and perianal region. On examination of oral cavity, tonsils were absent. On systemic examination, he had hepatosplenomegaly. Due to absent tonsils with recurrent infections and failure to thrive, he was suspected to be suffering from a Primary Immunodeficiency. His hemogram showed hemoglobin of 9.2 mg/dl with WBC count of 15,000/cumm [76% polymorphs, 8% Band Forms and 16% lymphocytes] with absolute lymphocyte count of 2400/cumm suggestive of lymphopenia and ESR of 12mm at end of 1 hour. His renal function test, liver function tests, urine and stool examination were normal. His urine culture was suggestive of candida albicans. X-Ray Chest revealed no thymic shadow. His HIV ELISA was negative. His serum immunoglobulins were all elevated [S. IgA = 100 mg/dl, S. IgG = 1426 mg/dl, S. IgM = 160 mg/dl] and CD panel by flow cytometry was suggestive of T- B+ NK- severe combined immunodeficiency most likely X-linked variant [CD3 = 20 cells/cumm, CD4 = 21 cells/cumm, CD8 = 24 cells/cumm, CD19 = 330 cells/cumm, CD20 = 437 cells/cumm, CD56 = 66 cells/cumm, CD16 = 630 cells/cumm]. He was treated with Intravenous Fluconazole and advised regarding Bone Marrow Transplant. In view of oral ulcers, skin rash along with hepatosplenomegaly he was suspected as a case of Graft versus host disease due to engraftment of maternal T cells. However it could not be confirmed by HLA testing as parents were not willing for the same.

Severe combined immunodeficiency (SCID) is characterized by abnormal T and B cell function from birth. It is the severest of all congenital immunodeficiencies and unless immunologic reconstitution is achieved through bone marrow transplantation or enzyme replacement, death usually occurs by 2 years of age. Several types of SCID have been identified and clinically classified as T-B+ or T-B- SCID depending on affection of B cells. T cells and subsets are low to absent in all types. X linked SCID is the commonest form of SCID and patients present as T-B+ NK- SCID (decreased T cells, normal B cell quantity and low Non-Killer cells) as was seen in our patient. Males are affected. Affected infants present with frequent episodes of diarrhea, pneumonia, sepsis and cutaneous infections within first few months of life. Failure to thrive after infections is common. Viral infections such as Varicella, Measles, Parainfluenzae, CMV, Epstein Barr Virus and fungal infections such as Candida, Pneumocystis Carinii (PCP) are common. Our patient had a candidial urinary tract infection. BCG vaccine can lead to disseminated TB. Infants lack the ability to reject foreign tissue and hence are at risk for graft-versus-host disease from maternal immunocompetent T cells or from T cells in non-irradiated blood transfusion or allogenic bone marrow transplant. Thymus tissue is hypoplastic and hypoplasia of adenoids, tonsils and peripheral lymph nodes is seen as was seen in our patient. Investigations reveal profound lymphopenia with diminished serum immunoglobulins and no antibody formation following investigation. Antibody levels may initially be normal due to passively transferred maternal antibodies. Analysis of lymphocyte subpopulation helps to identify the type of SCID. Treatment consists of bone marrow transplant. Gene therapy with enzyme replacement is useful in ADA deficient SCID.