The outcomes of alpha-mannosidosis after hematopoietic stem cell transplantation (HSCT) are incompletely described. This retrospective multi-center study evaluated the outcomes of patients who underwent HSCT for their alpha-mannosidosis after 2010. Twenty-one children (11 females) with enzymatically and/or genetically confirmed alpha-mannosidosis, diagnosed at a mean age of 14 months (0-60 months), were included. The median age at HSCT was 3.9 years (10 months to 13.3 years) with a median follow-up of 2.3 years (0.3-14.1 years). Seventy-four percent (14/19) of patients received an unrelated graft while the rest had a matched sibling donor. Primary engraftment was reached in 17 of 21 patients; four patients required a second HSCT with successful subsequent engraftment. Nine patients had severe post-HSCT infections, five patients developed acute graft-versus-host disease (GvHD) (> = grade II), and one patient had chronic GvHD. No patient died during follow-up. Seven out of ten patients received enzyme replacement therapy both pre- and post-HSCT. Among children with clinical symptoms, improvement was documented in hepatomegaly (40% of patients before HSCT, down to 10% after), recurrent infections (62%/30%), and hearing disorder (85%/65%). In 13 patients with developmental data, outcomes after HSCT suggested at least mild delays persisted post-HSCT in the majority (85%), with some trends of higher functioning with earlier treatment. Findings suggest HSCT has shown notable improvements in safety and is associated with clinical benefit in alpha-mannosidosis. Neurodevelopmental findings require longer-term study to account for phenotypic diversity.

Ankara Bilkent City Hospital Department of Pediatric Metabolism Ankara Türkiye

Ankara Bilkent City Hospital Health Sciences University Department of Pediatric Hematology Oncology and Pediatric Bone Marrow Transplantation Unit Ankara Türkiye

Ankara University Faculty of Medicine Department of Pediatric Hematology and Pediatric Bone Marrow Transplantation Unit Ankara Türkiye

Ankara University Faculty of Medicine Department of Pediatric Metabolism Ankara Türkiye

Ankara University Rare Diseases Application and Research Center Ankara Türkiye

Center for Inherited Metabolic Diseases Departments of Paediatrics and Adolescent Medicine and Clinical Genetics Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Center for Inherited Metabolic Disorders Department of Paediatrics National Institute of Children's Diseases and Faculty of Medicine Comenius University in Bratislava Bratislava Slovakia

Clinic of Medical Genetics and Prenatal Diagnostics Children's Clinical University Hospital Riga Latvia

Department of Biology and Microbiology Rīga Stradiņš University Riga Latvia

Department of Genetics and Genomics College of Medicine and Health Sciences United Arab Emirates University Al Ain United Arab Emirates and Department of Pediatrics Tawam Hospital Al Ain UAE

Department of Medical Genomics King Faisal Specialist Hospital and Research Centre Riyadh Kingdom of Saudi Arabia

Department of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University and Motol University Hospital Czech Republic

Department of Paediatrics University Medical Center Ulm Germany

Department of Pediatric Hematology and Oncology Children's Hospital of Brabois Vandœuvre lès Nancy France

Department of Pediatric Hematology and Pediatric Stem Cell Transplantation Unit Medicalpark Antalya Hospital Antalya Türkiye

Department of Pediatric Metabolism Ankara Yıldırım Beyazıt University Ankara Bilkent City Hospital Ankara Türkiye

Department of Pediatric Metabolism Ege University Faculty of Medicine İzmir Türkiye

Department of Pediatric Metabolism Reference Center of Inherited Metabolic Disorders Hôpital Jeanne de Flandre G2M sector Lille France

Department of Pediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Pediatrics Reference Center for Inborn Errors of Metabolism Filière G2M University Hospital of Nancy INSERM UMR_S 1256 NGERE University of Lorraine Nancy France

Division of Clinical Behavioral Neuroscience Department of Pediatrics University of Minnesota Medical School Minneapolis USA

Division of Paediatic Blood and Marrow Transplantation University of Minnesota Medical School Minneapolis USA

Division of Paediatric Hematology and Oncology Pediatric BMT Unit Ege University Faculty of Medicine İzmir Türkiye

Division of Pediatrics Department of Clinical Sciences Azienda Ospedaliero Universitaria delle Marche Presidio Salesi Ancona Italy

Heidelberg University Medical Faculty of Heidelberg Department of Pediatrics 1 Division of Pediatric Neurology and Metabolic Medicine Heidelberg Germany

J Inherit Metab Dis. 2025 Jul;48(4):e70068. doi: 10.1002/jimd.70068. PubMed

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