Novel AICDA mutation in a case of autosomal recessive hyper-IgM syndrome, growth hormone deficiency and autoimmunity

Allergol Immunopathol (Madr). 2017 Jan-Feb;45(1):82-86. doi: 10.1016/j.aller.2016.08.005. Epub 2016 Oct 24.

Abstract

Background: The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders, which have been rarely reported to be associated with growth hormone deficiency (GHD).

Methods and results: A nine-year-old girl with recurrent urinary tract infections, diarrhoea, sinopulmonary infections, and failure to thrive since the age of six months had normal CD3+, CD4+, CD8+T lymphocytes, and CD19+B lymphocytes and natural killer (NK) cells, but extremely elevated IgM and significantly decreased IgG and IgA. In view of the patient's short stature, growth hormone evaluation was carried out and growth hormone deficiency established. The patient underwent Ig replacement therapy and received growth hormone therapy in addition to antibiotics and responded well. Furthermore, the patient developed benign cervical lymphadenopathy, as well as elevated erythrocyte sedimentation rate, positive autoantibodies to SSA-Ro, and severely dry eyes, which partially responded to both the punctate occlusion and systemic corticosteroids, at the age of seven years. Sequencing analysis of the exons from activation-induced cytidine deaminase (AICDA) gene revealed that the patient was homozygous for a single T to C transversion at position 455 in exon 4, which replaces a Valine with an Alanine.

Conclusions: To our knowledge, this is a new AICDA mutation, which has not been reported previously in HIGM. The mutation analysis could improve diagnosis of HIGM patients and also elaborating on the spectrum of AICDA mutations.

Keywords: Autoimmunity; Class switch recombination; Growth hormone deficiency; Hyper-IgM syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Autoimmunity / genetics
  • Child
  • Cytidine Deaminase / genetics*
  • DNA Mutational Analysis
  • Dwarfism, Pituitary / genetics*
  • Female
  • Genotype
  • Growth Hormone / therapeutic use*
  • Hormone Replacement Therapy
  • Humans
  • Hyper-IgM Immunodeficiency Syndrome / genetics*
  • Immunoglobulin M / blood
  • Infant
  • Iran
  • Mutation, Missense / genetics*
  • Pedigree
  • Phenotype

Substances

  • Adrenal Cortex Hormones
  • Immunoglobulin M
  • Growth Hormone
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase

Supplementary concepts

  • Pituitary dwarfism 1