Background Previous studies have reported that NBAS gene-deficient diseases are caused by mutations in the NBAS gene. NBAS gene mutations could lead to SOPH syndrome, which clinically manifests as short stature, optic atrophy, and PH cells visible on peripheral blood smears, and can lead to recurrent liver failure induced by fever in children too. The clinical phenotypes fall into three categories: SOPH syndrome, fever-related liver failure, and intermediate phenotypes. However, most of these studies were retrospective in nature with small sample sizes, and maybe some of the phenotypes have not been identified. In this case, most characteristics were consistent with the clinical features of SOPH syndrome in patients with NBAS gene defects reported in the literature, but the immune damage was more extensive and involved multiple organ systems. Procedure The clinical data, auxiliary examination and gene mutation site of a case of NBAS gene deficiency disease combined with autoimmune thyroiditis and immune thrombocytopenia admitted to the Second Department of Hematology of Beijing Children’s Hospital were retrospectively analyzed. Results A 6-year-old male with neuroblastoma amplified sequence (NBAS) gene-defect disease complicated by autoimmune thyroiditis was admitted. During the disease course, fever, abnormal liver function, abnormal myocardial enzyme levels, and abnormal renal function were observed. Scattered hemorrhagic spots were observed all over the skin. Whole exon gene sequencing results showed NBAS heterozygous mutation c.3946dupT(p.W1316Lfs*5) in the father and c.5T>G(splicing) in the mother. Gamma globulin and glucocorticoids were used to restore normal platelet levels. Multisystem immune impairment may represent a new phenotype of NBAS mutations. The functions of all organs recovered after symptomatic treatment, and the functional index of the thyroid improved. Conclusion Immune impairment in multiple systems may be a novel phenotypic spectrum of mutations in NBAS genes.