title: Successful unrelated umbilical cord blood transplantation in Lesch-Nyhan syndrome.
abstract: Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation, delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation (HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable in LNS as well. Following a myeloablative conditioning regimen (busulphan 3.2 mg/kg/day for 4 days, cyclophosphamide 60 mg/kg/day for 2 days with ATG Thymoglobin 2.5 mg/kg/day for 4 days) an unrelated umbilical cord blood unit was transfused at the age of 2 years. The graft was a 6/6 HLA-matched at HLA-A, B loci by antigen level, and at DRB1 by allelic level typing. Infused total nucleated cell dose was 3.6 × 10e7 per kilogram body weight. Serum HPRT levels reached normal values by the end of the sixth month post transplant. Slow neurodevelopmental improvement seen during the three-year follow-up and the missing self-injuring behavior can be considered as a proof for the presence of enzyme-competent cells behind the blood-brain barrier.
authors.affiliation: Pediatric Hematology and Stem Cell Transplantation Unit, United St. István and St. László Hospital, Budapest, Hungary. kallay@ossejt.org
authors.forename: Krisztián
authors.initials: K
authors.lastname: Kállay
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Liptai
authors.forename: Gábor
authors.initials: G
authors.lastname: Benyó
authors.forename: Csaba
authors.initials: C
authors.lastname: Kassa
authors.forename: Veronika
authors.initials: V
authors.lastname: Goda
authors.forename: János
authors.initials: J
authors.lastname: Sinkó
authors.forename: Agnes
authors.initials: A
authors.lastname: Tóth
authors.forename: Gergely
authors.initials: G
authors.lastname: Kriván
mesh_terms: D002066:Busulfan / Q000627:therapeutic use; D002657:Child Development; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D004421:Dystonia / Q000209:etiology; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007926:Lesch-Nyhan Syndrome / Q000523:psychology / Q000628:therapy*; D008297:Male; D052016:Mucositis / Q000209:etiology / Q000473:pathology; D009128:Muscle Spasticity / Q000209:etiology; D009503:Neutropenia / Q000209:etiology; D016728:Self-Injurious Behavior / Q000209:etiology / Q000628:therapy
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D007041:Hypoxanthine Phosphoribosyltransferase; D002066:Busulfan