Umbilical cord blood transplantation for a patient with CHARGE syndrome and severe combined immunodeficiency

Abstract

CHARGE syndrome is a genetic disorder with congenital features, which is sometimes associated with immunodeficiency. We report a case of a patient with CHARGE syndrome with severe combined immunodeficiency (SCID) who underwent umbilical cord blood transplantation (CBT). The patient was referred for fatal growth retardation and delivered at 37 gestational weeks. He was diagnosed with CHARGE syndrome due to multiple malformations and deletion of CHD7. Since he was one month old, he had recurrent pneumonia and otitis media. Laboratory tests led to the diagnosis of T-B+NK+SCID. After the diagnosis, infections were effectively managed through intravenous immunoglobulin replacement therapy and prophylactic administration of antibiotics and antifungal agents. At 6 months old, he underwent 7/8 HLA allele-matched CBT without pre-conditioning. Tacrolimus and short methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. Subsequently, T-cell counts increased and the flow cytometry analysis revealed CD45RA-positive naive T cells on day 28. Grade 2 cutaneous acute GVHD occurred on day 14; however, it was immediately resolved by administering 2 mg/kg prednisolone. The treatment was tapered off 2 months post CBT without GVHD recurrence. Although thymic transplantation is the most suitable therapy for CHARGE syndrome with SCID, it is unavailable in most countries, including Japan. Recent reports have shown that CBT can successfully restore immune function and is expected to become an alternative treatment for SCID in patients with CHARGE syndrome.