title: 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.
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA; Children's National Medical Center, Washington, DC, USA.
authors.forename: Payal P
authors.initials: PP
authors.lastname: Khincha
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Wentzensen
authors.forename: Neelam
authors.initials: N
authors.lastname: Giri
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000728:Androgens / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019871:Dyskeratosis Congenita / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D016615:Telomere / Q000378:metabolism; D055815:Young Adult
chemical_list: D000728:Androgens
keywords: androgen; dyskeratosis congenita; telomere