Donor bone marrow from a sibling with inborn error of metabolism for treatment of acute leukaemia - clinical and biochemical consequences in the non-affected recipient

Bone marrow transplantation (BMT) is increasingly used in an attempt to cor rect inborn errors of metabolism (IEM), However, little is known about effe cts of BMT from patients with IEM donating for non-affected recipients. We present data from a 8.5-year-old girl who underwent BMT in second remission for relapsed acute lymphoblastic leukaemia (ALL) at the age of 7 years fro m her HLA-identical brother who was severely affected by Hunter syndrome (M ucopolysaccharidosis type II, iduronate-2-sulphatase (IDS) deficiency). Aft er BMT not only leukocyte but also plasma activity of IDS was absent. Mixin g experiments and immunoadsorption suggest antibody-mediated enzyme inhibit ion. However, her urinary glycosaminoglycan excretion has not increased pos t BMT and clinical signs of mucopolysaccharidosis are absent 20 months afte r BMT, We conclude that patients with white cell enzyme deficiencies and ot her IEMs do not have to be excluded from bone marrow donation. Antibody pro duction by the graft may occur and be reflected by a marked reduction in pl asma enzyme levels but not tissue activity. Similar antibody responses resu lting in enzyme inactivation might also affect other enzyme replacement str ategies for individuals with IEM.