Immundeficinecy 37 D81.4

Very rare autosomal recessive inherited (primary) combined immunodeficiency. IMD37 is characterized by hypogammaglobulinemia without lymphopenia, but with severely decreased numbers of memory B cells and memory T cells and increased numbers of circulating naive lymphocytes. Furthermore, the phenotpy was characterized by status epilepticus (Xue L et al 2003) .

Homozygous or compound heterozygous mutation in the BCL10 gene (BCL10 immune signaling adaptor) located on chromosome 1p22.3.

An autosomal recessive LOF- BCL10 mutation with complete BCL10 deficiency results in a comprehensive immunodeficiency. The defect included both hematopoietic and non-hematopoietic immunity.

An autosomal recessive LOF- BCL10 mutation with complete BCL10 deficiency resulted in severe primary combined immunodeficiency disease in a boy from Ecuador born to consanguineous parents. This resulted in death at age three from encephalitis. One sister died of infection at 6 months of age (Torres JM 2014) .

Clinically, gastroenteritis, otitis media, and recurrent respiratory infections continued to present. At 8 months of age, he had a severe viral influenza infection, respiratory syncytial virus (RSV) infection, and oral and enteric Candida infections. Later, infections with Campylobacter jejuni, adenovirus, and Clostridium difficile followed. Furthermore, seizures with status epilepticus presented.

Laboratory tests revealed hypogammaglobulinemia without lymphopenia, severely decreased memory B cells and memory T cells, and an increased number of circulating naive lymphocytes.

1. Goel S et al (2022) CARD9 Expression Pattern, Gene Dosage, and Immunodeficiency Phenotype Revisited. J Clin Immunol 42:336-349.
2. Torres JM (2014) Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity. J Clin Invest 124:5239-5248.
3. Xue L et al (2003) Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells. Nature Immun 4: 857-865.