Immunodeficiency 12D81.4

Rare primary immunodeficiency caused by mutations in the MALT1 gene. Clinically, immunodeficiency is characterized by recurrent bacterial, viral and mycotic infections (pathogens: Pseudomonas, Streptococcus, Haemophilus influenza, Klebsiella and Cytomegalovirus) in infancy, resulting in bronchiectasis and growth retardation. Clinical manifestations include: mastoiditis, aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, duodenitis and meningitis.

Laboratory tests often reveal normal levels of absolute lymphocytes and immunoglobulins in serum. Specific antibody titers remain low despite immunization, and T cells show an impaired proliferative response to mitogens. IgE may be elevated.

If left untreated, patients die in childhood or adolescence.

Jabara et al (2013) reported on two siblings of consanguineous Lebanese parents with a primary immunodeficiency that began in infancy with recurrent bacterial and Candida infections and led to bronchiectasis and growth retardation. Manifestations included mastoiditis, aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, duodenitis, and meningitis. Pathogens included pseudomonas, streptococcus, Haemophilus influenza, Klebsiella, and cytomegalovirus (CMV). The patients died at ages 7 and 13.5 years. Laboratory tests revealed normal levels of absolute lymphocytes and immunoglobulins in serum, but specific antibody titers were low despite immunization, and T cells showed an impaired proliferative response to mitogens.

McKinnon et al (2014) reported on a 15-year-old girl born to consanguineous Kurdish parents who was diagnosed with severe primary immunodeficiency since infancy. She had recurrent chronic dermatitis, inflammatory gastrointestinal disease, and recurrent pneumonia leading to bronchiectasis. Pathogens included Staphylococcus aureus, varicella virus, herpes simplex virus, streptococcus, and CMV. The patient also had nonspecific dysmorphic facial features and delayed bone age with osteoporosis. Immunophenotyping of the patient's B cells revealed increased numbers of naïve B cells, absent marginal zone B cells, and decreased numbers of switched memory B cells, suggesting arrested B cell development. However, serum Ig levels were normal, with the exception of elevated IgE, and the patient was able to produce antibodies to vaccines. CD3+ T cells were elevated, with a predominance of the CD4+ T helper subset. Although absolute lymphocyte counts were normal, stimulation tests showed a lack of proliferation and blast formation in CD3+ T cells.

1. Jabara HH et al. (2013) A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency. J. Allergy Clin. Immun. 132: 151-158, 2013. note: erratum: J Allergy Clin Immun 132: 773.
2. McKinnon ML et al (2014) Combined immunodeficiency associated with homozygous MALT1 mutations. (Letter) J Allergy Clin Immun 133: 1458-1462.