Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications.
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.
Hönig
Manfred
M
Department of Pediatrics, University of Ulm, University Clinic for Child and Adolescent Medicine, Eythstrasse 24, 89075 Ulm, Germany.
Albert
Michael H
MH
Schulz
Ansgar
A
Sparber-Sauer
Monika
M
Schütz
Catharina
C
Belohradsky
Bernd
B
Güngör
Tayfun
T
Rojewski
Markus T
MT
Bode
Harald
H
Pannicke
Ulrich
U
Lippold
Dominique
D
Schwarz
Klaus
K
Debatin
Klaus-Michael
KM
Hershfield
Michael S
MS
Friedrich
Wilhelm
W
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
D000243:Adenosine Deaminase