A Chinese DADA2 patient: report of two novel mutations and successful HSCT

Immunogenetics. 2019 Apr;71(4):299-305. doi: 10.1007/s00251-018-01101-w. Epub 2019 Jan 5.

Abstract

Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by autosomal recessive mutations in Cat Eye Syndrome Chromosome Region 1 (CECR1) gene. In this report, we aimed to describe the clinical manifestations, immunological features, genotype, and treatments of one Chinese patient with novel CECR1 gene mutations. This patient initially presented with recurrent fever and rashes from the age of 3 months, but no pathogen was found. She then developed dry gangrene of the fingers at 5 months of age. Laboratory examinations revealed elevated levels of C-reactive protein and thrombocytes. The expression of interleukin-6 (IL-6) and IL-8 were both elevated. Sequencing results revealed that she had compound heterozygous mutations in CECR1 gene (c.1211T>C, p.Phe404Ser and c.1114 G>A, p.Val372Met). Subsequently, treatment with anti-IL-6 (tocilizumab) was started. However, she developed blurred vision in the right eye with occlusion of the central retinal artery, accompanied by unsteady gait. Magnetic resonance imaging (MRI) showed infarction of the right thalamus. Finally, she underwent hematopoietic stem cell transplantation (HSCT) and is currently in remission. Our findings suggest that HSCT could cure this disease.

Keywords: Adenosine deaminase 2 deficiency; CECR1 gene; Hematopoietic stem cell transplantation; Novel mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / deficiency*
  • Adenosine Deaminase / genetics
  • Agammaglobulinemia / diagnostic imaging
  • Agammaglobulinemia / genetics
  • Agammaglobulinemia / therapy*
  • Asian People
  • Base Sequence
  • China
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hereditary Autoinflammatory Diseases / diagnostic imaging
  • Hereditary Autoinflammatory Diseases / genetics
  • Hereditary Autoinflammatory Diseases / therapy*
  • Humans
  • Infant
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Magnetic Resonance Imaging
  • Mutation*
  • Remission Induction
  • Sequence Analysis, DNA
  • Severe Combined Immunodeficiency / diagnostic imaging
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / therapy*

Substances

  • Intercellular Signaling Peptides and Proteins
  • ADA2 protein, human
  • Adenosine Deaminase

Supplementary concepts

  • Severe combined immunodeficiency due to adenosine deaminase deficiency