Dyskeratosis Congenita: Multisystemic Disorder with Special Consideration of Immunologic Aspects

Abstract

Dyskeratosis congenita (DC) is a rare, predominantly X-linked multisystemic disorder. It demonstrates a wide spectrum of clinical manifestations and typically presents with dermatologic symptoms during the first decade of life. This review of the literature points out the importance of hematologic and immunologic alterations in defining the course and prognosis of the disease process. Pancytopenia as well as the humoral and cellular disturbances in immunologic functions associated with this disease complex may lead to severe infections that represent the main cause of death. The pathogenesis of DC is still unclear and a curative therapy is presently lacking. Recent reports suggest that a beneficial effect may be observed in the administration of hematopoietic growth factors (G-CSF, GM-CSF) for patients with DC and neutropenia.

Association of immune abnormalities with telomere shortening in autosomal-dominant dyskeratosis congenita

“…These immune abnormalities were primarily humoral, with a significant decrease in B-cell number, low IgM serum levels, and elevated IgA levels in 9 of 10 subjects tested. A variable pattern of similar immune abnormalities 5,6,14 has previously been observed in X-linked DC. The findings of this study therefore further develop the functional link between these 2 subtypes of DC.…”

“…A variable immune deficiency has also been described in the X-linked form of the disease. 5,6 In some cases of X-linked DC, the immune deficiency is very severe and has been categorized as "TϩB-NK SCID," 14 where SCID indicates severe combined immunodeficiency. Since reporting the TERC mutation as the underlying molecular basis for AD DC 1 we have been closely following a large 3-generation-affected kindred.…”

“…In X-linked DC, various B-and T-cell abnormalities have been reported. 5 In a recent review of patients with DC, elevated, normal, and reduced immunoglobulin G (IgG) levels were noted in 38%, 45%, and 17% of patients, respectively. 6 Similarly, B-cell counts were normal in 41% of patients but were reduced in 59% of patients.…”

A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish

“…The regulation of CSF genes by TR might have important clinical implications, since GCSF and GMCSF therapy has been used in DC patients to treat neutropenia 47 . It is tempting to speculate, therefore, that this therapy might be specifically efficient in DC patients carrying mutations in the TR gene before telomeres are critically short in HSC.…”

Telomerase in T Lymphocytes: Use It and Lose It?

“…The leukocytes from patients with both forms of the disease have short telomeres and reduced T and B cell numbers compared with age-matched controls (49), which further underscores the link between lack of telomerase activity and telomere erosion in lymphocytes. Furthermore, 50% of these pa- (49). These patients were susceptible to recurrent infections and even opportunistic infections such as Pneumocystis carinii pneumonia (49).…”