Patients with severe combined immunodeficiency (SCID) usually presents with severe infections. This case is presented to highlight the severe autoimmune manifestation, sever microcephaly and disseminated CMV infection in a child with SCID.
A 2-month-old boy, born to a consanguineous marriage, presented with a generalized erythematous rash and recurrent diarrhoea. At 7 months of age, he developed respiratory distress. At 9 months of age, he started developing recurrent episodes of anaemia requiring packed red cell transfusions. Physical examination revealed failure to thrive and significant microcephaly, bilateral undescended testes, spleno-hepatomegaly and bilateral chest crepitations.
He had anemia and thrombocytopenia. Absolute lymphocyte count was 2.14 x109/L. Peripheral blood smear revealed signs of haemolysis and positive Direct Coombs Test. Blood CMV PCR was positive and viral load was 56722 copies/ml. IgG- 3.33 g/L (3.7-15.80), IgA - <0.17 g/L (0.30-1.30), IgM- 1.19 g/L (0.60-1.20) and IgE <2 IU/ml (up to 32). Lymphocyte subsets showed markedly reduced B cells. Flowcytometry showed CD4/CD8 reversal, decreased naïve T cells, increased HLA DR expression on CD3+ T cells. For autoimmune hemolytic anemia, intravenous immunoglobulin (IVIg) 1 gm/kg was given and also required high dose steroids. He required additional therapy IVIg and oral sirolimus (at 1 mg/m2), following which there was gradual recovery. Possibility of SCID was considered. Whole exome sequencing revealed frameshift mutation in NHEJ1 c.544_545delGA, p.Glu182fs.
Severe microcephaly and growth retardation in context of SCID can be clue toward diagnosis. In patients with refractory severe autoimmune haemolytic anemia, one may consider addition of sirolimus.