Response to androgen therapy in patients with dyskeratosis congenita

Abstract

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and telomere biology disorder characterized by dysplastic nails, reticular skin pigmentation and oral leucoplakia. Androgens are a standard therapeutic option for bone marrow failure in those patients with DC who are unable to undergo haematopoietic stem cell transplantation, but there are no systematic data on its use in those patients. We evaluated haematological response and side effects of androgen therapy in 16 patients with DC in our observational cohort study. Untreated DC patients served as controls. Seventy percent of treated DC patients had a haematological response with red blood cell and/or platelet transfusion independence. The expected age-related decline in telomere length was noted in androgen-treated patients. All treated DC patients had at least one significant lipid abnormality. Additional treatment-related findings included a significant decrease in thyroid binding globulin, accelerated growth in pre-pubertal children and splenic peliosis in two patients. Liver enzymes were elevated in both androgen-treated and untreated patients, suggesting underlying liver involvement in DC. This study suggests that androgen therapy can be effectively used to treat bone marrow failure in DC, but that side effects need to be closely monitored.

Keywords: androgen; dyskeratosis congenita; telomere.

Conflict of interest statement

DISCLOSURE OF CONFLICTS OF INTEREST

The authors declare no conflict of interest.

Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Figures

Figure 1. Haematological response in all patients with DC treated with androgens

The median is denoted by the solid horizontal line. A) Haemoglobin (g/l) B) Absolute Neutrophil Count (× 109/l) C) Platelet count (× 109/l) DC, dyskeratosis congenita

Figure 1. Haematological response in all patients with DC treated with androgens

The median is denoted by the solid horizontal line. A) Haemoglobin (g/l) B) Absolute Neutrophil Count (× 109/l) C) Platelet count (× 109/l) DC, dyskeratosis congenita

Figure 1. Haematological response in all patients with DC treated with androgens

The median is denoted by the solid horizontal line. A) Haemoglobin (g/l) B) Absolute Neutrophil Count (× 109/l) C) Platelet count (× 109/l) DC, dyskeratosis congenita

Figure 2. Longitudinal telomere lengths in patients with DC

A) Pre- and post-androgen lymphocyte telomere lengths in 4 DC patients. The green line indicates the patient treated with fluoxymesterone. The other three patients received oxymetholone. Legend reflects the known germline mutation in each patient. B) Lymphocyte telomere lengths in 5 DC patients not treated with androgens. Legend reflects the known germline mutation in each patient. DC, dyskeratosis congenita

Figure 2. Longitudinal telomere lengths in patients with DC

A) Pre- and post-androgen lymphocyte telomere lengths in 4 DC patients. The green line indicates the patient treated with fluoxymesterone. The other three patients received oxymetholone. Legend reflects the known germline mutation in each patient. B) Lymphocyte telomere lengths in 5 DC patients not treated with androgens. Legend reflects the known germline mutation in each patient. DC, dyskeratosis congenita

Figure 3. Summary of lipid changes in patients with DC and FA treated with androgens

DC, dyskeratosis congenita; FA, Fanconi anaemia; HDL, high density lipoprotein; LDL, low density lipoprotein

Figure 4. Growth acceleration in six pre-pubertal male dyskeratosis congenita patients on androgen therapy

Growth charts from CDC website, May 2000 (http://www.cdc.gov/growthcharts/clinical_charts.htm). Legend reflects the known germline mutation in each patient.