biostudies-literatureUnknown24Mhanni AAChildren&apos;s Hospital Research Institute of ManitobaEnzyme replacement therapy (ERT) has been shown to stabilize certain aspects of Fabry disease (FD). However, in some patients on ERT, high antibody titres have been documented, with limited clinical improvement in systemic manifestations and often with significant adverse drug reactions. We present two related adolescent males with a 4.5 kb <i>GLA</i> deletion, not amenable to chaperone therapy, leading to profound reduction in α-galactosidase A (α-gal A) enzyme activity. Over a 3-year period of ERT, increasing IgG antibody titres against α-gal A were noted. After starting ERT serial urine globotriaosylceramide (Gb₃) measurements showed an upward trend from 333 to 2260 μg/mmol creatinine for patient 1 and 1165 to 2260 μg/mmol creatinine for patient 2. Markedly increased levels oMolecular genetics and metabolism reports100618https://www.ebi.ac.uk/biostudies/studies/S-EPMC7322173biostudies-literatureTherapeutic challenges in two adolescent male patients with Fabry disease and high antibody titres.PMC7322173Auray-Blais CWest MLMhanni AABoutin MPatterson JAerts JMFGRockman-Greenberg CLeMoine KJohnston AfalseTherapeutic challenges in two adolescent male patients with Fabry disease and high antibody titres.Enzyme replacement therapy (ERT) has been shown to stabilize certain aspects of Fabry disease (FD). However, in some patients on ERT, high antibody titres have been documented, with limited clinical improvement in systemic manifestations and often with significant adverse drug reactions. We present two related adolescent males with a 4.5 kb <i>GLA</i> deletion, not amenable to chaperone therapy, leading to profound reduction in α-galactosidase A (α-gal A) enzyme activity. Over a 3-year period of ERT, increasing IgG antibody titres against α-gal A were noted. After starting ERT serial urine globotriaosylceramide (Gb₃) measurements showed an upward trend from 333 to 2260 μg/mmol creatinine for patient 1 and 1165 to 2260 μg/mmol creatinine for patient 2. Markedly increased levels o2020-01-01T00:00:00Z2020 Sep2026-04-07T18:51:55.106Z2020-07-04T07:22:31ZS-EPMC73221733261293310.1016/j.ymgmr.2020.100618