1. Antibody Deficiency in Patients with Biallelic KARS1 Mutations
- Author
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Saettini, F, Guerra, F, Fazio, G, Bugarin, C, Mcmillan, H, Ohtake, A, Ardissone, A, Itoh, M, Giglio, S, Cappuccio, G, Giardino, G, Romano, R, Quadri, M, Gasperini, S, Moratto, D, Chiarini, M, Akira, I, Fukuhara, Y, Hayakawa, I, Okazaki, Y, Mauri, M, Piazza, R, Cazzaniga, G, Biondi, A, Saettini F., Guerra F., Fazio G., Bugarin C., McMillan H. J., Ohtake A., Ardissone A., Itoh M., Giglio S., Cappuccio G., Giardino G., Romano R., Quadri M., Gasperini S., Moratto D., Chiarini M., Akira I., Fukuhara Y., Hayakawa I., Okazaki Y., Mauri M., Piazza R., Cazzaniga G., Biondi A., Saettini, F, Guerra, F, Fazio, G, Bugarin, C, Mcmillan, H, Ohtake, A, Ardissone, A, Itoh, M, Giglio, S, Cappuccio, G, Giardino, G, Romano, R, Quadri, M, Gasperini, S, Moratto, D, Chiarini, M, Akira, I, Fukuhara, Y, Hayakawa, I, Okazaki, Y, Mauri, M, Piazza, R, Cazzaniga, G, Biondi, A, Saettini F., Guerra F., Fazio G., Bugarin C., McMillan H. J., Ohtake A., Ardissone A., Itoh M., Giglio S., Cappuccio G., Giardino G., Romano R., Quadri M., Gasperini S., Moratto D., Chiarini M., Akira I., Fukuhara Y., Hayakawa I., Okazaki Y., Mauri M., Piazza R., Cazzaniga G., and Biondi A.
- Abstract
Biallelic KARS1 mutations cause KARS-related diseases, a rare syndromic condition encompassing central and peripheral nervous system impairment, heart and liver disease, and deafness. KARS1 encodes the t-RNA synthase of lysine, an aminoacyl-tRNA synthetase, involved in different physiological mechanisms (such as angiogenesis, post-translational modifications, translation initiation, autophagy and mitochondrial function). Although patients with immune-hematological abnormalities have been individually described, results have not been collectively discussed and functional studies investigating how KARS1 mutations affect B cells have not been performed. Here, we describe one patient with severe developmental delay, sensoneurinal deafness, acute disseminated encephalomyelitis, hypogammaglobulinemia and recurrent infections. Pathogenic biallelic KARS1 variants (Phe291Val/ Pro499Leu) were associated with impaired B cell metabolism (decreased mitochondrial numbers and activity). All published cases of KARS-related diseases were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Seventeen patients with KARS-related diseases were identified. Recurrent/severe infections (9/17) and B cell abnormalities (either B cell lymphopenia [3/9], hypogammaglobulinemia [either IgG, IgA or IgM; 6/15] or impaired vaccine responses [4/7]) were frequently reported. Immunoglobulin replacement therapy was given in five patients. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment.
- Published
- 2023