Actin-related protein 2/3 complex subunit 1B (ARPC1b) is an important molecule for cytoskeletal dynamics. Loss-of-function mutations in the ARPC1b gene have been shown to disrupt protein structure, causing an autosomal recessive syndrome of combined immunodeficiency. Reported phenotypes include impaired T cell migration and proliferation, recurrent sinopulmonary infections, colitis, elevated IgA and IgE, and platelet abnormalities.
We present a case of a 17-year-old female with a new diagnosis of ARPC1b deficiency (homozygous c.783G>A p.Ala261) manifesting with combined immunodeficiency. She was born to consanguineous parents of Afghani background and arrived in Australia aged 15 under refugee status. There is no known family history of immunodeficiency. From 10 days of life, she had a history of episodic haematochezia until aged 14. In addition, there was a history of previous menorrhagia with reported thrombocytopaenia (now ceased). She has a persistent long-standing history of recurrent sinopulmonary infections with more recent skin abscesses. She also has a history of bilateral sensorineural hearing loss. Immunological investigations showed reduced platelet volumes (5.2–6.3 fL) without persistent thrombocytopaenia. She has had persistent CD4 and CD8 lymphopenia, low naïve T cells (7.6%), and normal T cell proliferation (phytohemagglutinin). She has a high IgG and IgM, with low IgA and mildly elevated IgE. There was a poor serological response to 23-valent pneumococcal polysaccharide vaccination. She had no evidence of bronchiectasis on high-resolution CT. She underwent genetic next-generation sequencing (NGS) and was found to have a homozygous c.783G>A p.Ala261 variant in the ARPC1b gene. Interestingly, there has been an attenuation in her phenotype since arriving in Australia with no further haematochezia and thrombocytopaenia without treatment. Further genetic evaluation is underway to assess for the possibility of somatic reversion. She was started on cotrimoxazole prophylaxis and intravenous immunoglobulin and has been referred for consideration of haematopoietic stem cell transplant.
