Congenital T- and NK-cell immunodeficiency with impaired expression of β-integrin on neutrophils in a patient with a mutation in the KMT2D gene: a description of a clinical case

Abstract

Background. Pathogenic mutations in the KMT2D or KDM6A genes are associated not only with the classic manifestations of Kabuki syndrome (KS), characterized by postnatal growth failure, dysmorphic facial features, skeletal anomalies, and mental retardation, but are also characterized by manifestations of common variable immunodeficiency, detected in at least 50 % patients. Persons with KS have a tendency to recurrent infections, primarily of the ENT organs, and hypogammaglobulinemia.

Aim – to demonstrate the difficulties of diagnosing the causes of congenital immunodeficiency in children and present a diagnostic search algorithm.

Material and methods. A child from the second birth at term from nonconsanguineous parents. The elder sister is healthy. Psychomotor development up to 12 months was normal. From the age of 14 months experienced purulent conjunctivitis, pharyngitis and rhinitis, resistant to ongoing therapy. At the age of 16 months unsteady gait, increasing muscle hypotension, periodic obsessive hand movements by the type of hyperkinesis were noted. Microcephaly with a head circumference 44 cm (< 5th centile). He was hospitalized with bilateral pneumonia, purulent conjunctivitis, left-sided otitis media.

Results. The absence of T-regulatory cells (CD4+CD25highCD127) and effector NK cells (CD16+CD56+CD3) in the peripheral blood with a decrease in CD4 levels resulting in granulomatous lung damage, proved by biopsy, enterocolitis and pansinusitis was revealed. The levels of CD4+CD3+-T-lymphocytes and CD4+/CD8+ index were also decreased. In addition, integrin-beta (CD18) expression was absent on granulocytes. Whole exome sequencing revealed a deletion in exon 24 of the KMT2D gene, which made it possible to make an accurate clinical diagnosis of kabuki syndrome. At the same time, the patient did not have characteristic hypogammaglobulinemia and dysmorphic features.

Conclusion. Severe infection is not always the primary clinical manifestation of some rare forms of congenital immunodeficiencies. The debut may be associated with non-infectious features, which does not exclude the presence of a congenital genetic defect, determining further a combination of clinical syndromes and requiring complex therapy and interaction of doctors of various specialties.

Keywords:T- and NK-cell immunodeficiency; integrin beta (CD18); KMT2D mutation; granulomatous lymphocytic interstitial lung disease

For citation: Dolgopolov I.S., Kochegurova E.M., Grivtsova L.Yu., Ustinova O.K., Rykov M.Yu. Congenital T- and NK-cell immunodeficiency with impaired expression of β-integrin on neutrophils in a patient with a mutation in the KMT2D gene: a description of a clinical case. Immunologiya. 2022; 43 (2): 137–48. DOI: https://doi.org/10.33029/0206-4952-2022-43-2-137-148 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

Authors’ contributions: development of the concept of scientific work, statistical processing, compilation of a draft manuscript, final approval of the published version of the manuscript – Dolgopolov I.S.; text writing, planning and analysis of scientific work – Kochegurova E.M., Grivtsova L.Yu., Ustinova O.K.; text writing, analysis of scientific work, critical revision with the introduction of valuable intellectual content, final approval of the published version of the manuscript – Rykov M.Yu.

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