CHARGE syndrome is caused by pathogenic variants in the CHD7 gene and is characterized by coloboma, congenital heart defects, choanal atresia, growth retardation/developmental delay, genital hypoplasia, and ear anomalies with hearing loss. CHARGE syndrome with athymia can present with complete absence of the thymus, leading to T cell deficiency and a clinical phenotype of severe combined immunodeficiency (SCID). Early therapeutic intervention is required after diagnosis. Thymic transplantation is the curative treatment; however, when access is limited, hematopoietic stem cell transplantation (HSCT) may be an alternative. In Japan, reports of cord blood transplantation for CHARGE syndrome with athymia are limited, and cases diagnosed and treated before infectious complications through newborn screening (NBS) are extremely rare.
A male infant was born at 41 weeks’ gestation, weighing 3,632 g. Expanded NBS at day 6 revealed T cell receptor excision circle (TREC) 0 copies, reported on day 16. Positive-pressure management, cessation of breastfeeding, antifungal and anti-CMV prophylaxis, and immunoglobulin replacement were promptly initiated. Genetic testing identified a known frameshift variant in CHD7, and together with imaging findings of thymic aplasia, the patient was diagnosed with CHARGE syndrome with athymia. On day 30, he underwent aortic arch repair for coarctation of the aorta. On day 66, he received a 7/8 HLA allele–matched cord blood transplant without conditioning. T cells appeared in peripheral blood on day 14 post-transplant. At 1 month, he developed stage 2 skin graft versus host disease (GVHD), currently managed with adjustment of immunosuppressive therapy; no other transplant-related complications or infections have occurred.
Although long-term outcomes after HSCT require further follow-up, this case demonstrates that diagnosis of CHARGE syndrome with athymia by NBS prior to infectious complications enabled early appropriate supportive care and treatment planning, which likely contributed to a reduced risk of transplant-related mortality.
