Background: Although severe T cell immunodeficiency in DiGeorge anomaly is rare, previous studies of humoral function in these patients have found no antibody abnormalities but have not examined the response to polysaccharide antigens. Isolated cases of autoimmunity have been reported. Several patients with 22q11.2 deletion attending our immunology clinic suffered recurrent sinopulmonary infection or autoimmune phenomena. Aims: To investigate humoral immunodeficiency, particularly pneumococcal polysaccharide antibody deficiency, and autoimmune phenomena in a cohort of patients with 22q11.2 deletion. Methods: A history of severe or recurrent infection and autoimmune symptoms were noted. Lymphocyte subsets, immunoglobulins, IgG subclasses, specific vaccine antibodies, and autoantibodies were measured. Subjects were vaccinated with appropriate antigens as indicated. Results: Of 32 patients identified, 26 (81%) had severe or recurrent infection, of which 13 (50%) had abnormal serum immunoglobulin measurements and 11/20 >4 years old (55%) had an abnormal response to pneumococcal polysaccharide. Ten of 30 patients (33%) had autoimmune phenomena; six (20%) were symptomatic. Conclusions: Humoral immunodeficiency is more common than previously recognised in patients with 22q11.2 deletion. Normal T cell function and immunoglobulin levels do not exclude poor specific antibody responses. Patients should be referred for formal immunological assessment of cellular and humoral immune function.

Children with primary immunodeficiency diseases, particularly those less than 1 year of age, experience significant toxicity after hematopoietic stem cell transplantation, with busulfan-or melphalan-based conditioning. Treosulfan causes less venoocclusive disease than busulfan and does not require pharmacokinetic monitoring. We report its use in 70 children.

SummaryMore than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are associated with T-B + NK + SCID phenotype. Severe immunodeficiency with CHARGE syndrome has been noted only rarely Omenn syndrome is a rare autosomal recessive form of SCID with erythroderma, hepatosplenomegaly, lymphadenopathy and alopecia. Hypomorphic recombination activating genes 1 and 2 mutations were first described in patients with Omenn syndrome. More recently, defects in Artemis, RMRP, IL7Ra and common gamma chain genes have been described. We describe four patients with mutations in CHD7, who had clinical features of CHARGE syndrome and who had T-B + NK + SCID (two patients) or clinical features consistent with Omenn syndrome (two patients). Immunodeficiency in patients with DiGeorge syndrome is well recognized -CHARGE syndrome should now be added to the causes of T-B + NK + SCID, and mutations in the CHD7 gene may be associated with Omenn-like syndrome.

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Summary:Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT), is frequently associated with total body irradiation (TBI) given in the pre-BMT conditioning protocol. We report our preliminary observation of the prevalence of thyroid dysfunction in children transplanted for primary immunodeficiency (PID) who were given cytoreductive conditioning with busulphan and cyclophosphamide, but without TBI. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (fT4) in 83 survivors transplanted between 1987 and 2002. We found nine children (10.8%) with clinical and/or biochemical thyroid dysfunction at 4 months to 4.5 years post-BMT of which three had positive antithyroid microsomal antibodies. Two patients were classified as primary and seven as compensated hypothyroidism (hyperthyrotropinaemia). Four patients with clinical features of hypothyroidism received replacement thyroxine, while five of the seven patients with compensated hypothyroidism remain off thyroxine because we suspect this may be a transient phenomenon. Abnormalities of thyroid function including severe primary hypothyroidism may occur post-BMT in children receiving chemotherapy conditioning without TBI. Thyroid function should be assessed regularly in this group of patients.