Refractory and Fatal Presentation of Severe Autoimmune Hemolytic Anemia in a Child With the DNASE1L3 Mutation Complicated With an Additional DOCK8 Variant.


Paç K. , Witzel M., Unal E. , Rohlfs M., Akyildiz B. , Dogan M. E. , ...More

Journal of pediatric hematology/oncology, vol.43, no.3, 2021 (Journal Indexed in SCI Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 43 Issue: 3
  • Publication Date: 2021
  • Doi Number: 10.1097/mph.0000000000001780
  • Title of Journal : Journal of pediatric hematology/oncology
  • Keywords: monogenic lupus, immune deficiency, genetic, PRIMARY IMMUNODEFICIENCY, DEFICIENCY, RECOMMENDATIONS, VASCULITIS, PHENOTYPE, DIAGNOSIS, LESSONS, BOY

Abstract

Various autoimmune diseases may be associated with primary immune deficiencies. We reported a case with a loss-of-function mutation in DNASE1L3, a gene described previously in families with systemic lupus erythematosus. In addition, the patient showed a novel homozygous missense variant in DOCK8, a gene known to be responsible for the hyper-IgE recurrent infection syndrome (HIES). A 3-year-old girl born to consanguine parents presented with chronic urticarial rash, hemolytic anemia, pulmonary hemorrhage, and hypovolemic shock findings. She had a low hemoglobin level, a positive direct antiglobulin test, antinuclear antibody and anti-double stranded DNA, low C3 and C4, third-degree tricuspid regurgitation, and severe enlargement of the right ventricle on echocardiography, suggesting pulmonary embolism. Despite treatment with intravenous immunoglobulin, pulse metilprednisolone, rituximab, and supportive treatment for shock, the patient died on the seventh day. Whole-exome sequencing indicated a homozygous stop variant c.537G>A (p. Trp179Ter) in DNASE1L3. In addition, a possibly pathogenic homozygous missense variant in the HIES gene DOCK8 was detected. The occurrence of potentially clinically relevant, genetic variants in several genes posed various challenges with respect to diagnosis, treatment, and prognosis.