title: Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications.
abstract: Adenosine deaminase (ADA) deficiency is a systemic metabolic disease that causes an autosomal recessive variant of severe combined immunodeficiency (SCID) and less consistently other complications including neurologic abnormalities. Hematopoietic stem cell transplantation (HSCT) is able to correct the immunodeficiency, whereas control of nonimmunologic complications has not been extensively explored. We applied HSCT in 15 ADA-deficient patients consecutively treated at our institutions since 1982 and analyzed long-term outcome. Seven patients received transplants without conditioning from HLA-matched family donors (MFDs); the other 8 patients received conditioning and were given transplants either from HLA-mismatched family donors (MMFDs; n = 6) or from matched unrelated donors (MUDs; n = 2). At a mean follow-up period of 12 years (range, 4-22 years), 12 patients are alive with stable and complete immune reconstitution (7 of 7 after MFD, 4 of 6 after MMFD, and 1 of 2 after MUD transplantation). Six of 12 surviving patients show marked neurologic abnormalities, which include mental retardation, motor dysfunction, and sensorineural hearing deficit. We were unable to identify disease or transplantation-related factors correlating with this divergent neurologic outcome. The high rate of neurologic abnormalities observed in long-term surviving patients with ADA deficiency indicates that HSCT commonly fails to control CNS complications in this metabolic disease.
authors.affiliation: Department of Pediatrics, University of Ulm, University Clinic for Child and Adolescent Medicine, Eythstrasse 24, 89075 Ulm, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hönig
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schulz
authors.forename: Monika
authors.initials: M
authors.lastname: Sparber-Sauer
authors.forename: Catharina
authors.initials: C
authors.lastname: Schütz
authors.forename: Bernd
authors.initials: B
authors.lastname: Belohradsky
authors.forename: Tayfun
authors.initials: T
authors.lastname: Güngör
authors.forename: Markus T
authors.initials: MT
authors.lastname: Rojewski
authors.forename: Harald
authors.initials: H
authors.lastname: Bode
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pannicke
authors.forename: Dominique
authors.initials: D
authors.lastname: Lippold
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hershfield
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Friedrich
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency*; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019520:Living Donors; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology* / Q000401:mortality; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000150:complications* / Q000401:mortality / Q000628:therapy*; D014184:Transplantation, Homologous
chemical_list: D000243:Adenosine Deaminase