Original ArticlesEffective treatment of α-mannosidosis by allogeneic hematopoietic stem cell transplantation☆
Section snippets
Patients
This study includes all 4 patients with α-mannosidosis transplanted at the University of Minnesota. These transplants were performed between January 1997 and October 2002, with follow-up through October 2003. Diagnosis was confirmed by measurement of leukocyte acid α-mannosidase. Clinical features before HCT are summarized in Table I.
Conditioning regimen and donor grafts
The conditioning regimen consisted of one of the following (1) Bu/Cy/ATG/TBI: 320 mg/m2 busulfan PO, 120 mg/kg cyclophosphamide IV, 60 mg/kg antithymocyte globulin
Results
After HCT, all 4 patients are alive with follow-up after HCT at 6 years, 6 years, 4 years, and 1 year, respectively. All four patients show complete donor-derived engraftment and normalization of leukocyte α-mannosidase activity (>170 nmol/h per milligram of protein) for the duration of follow-up. All patients had acute GVHD, and patient 3 also had chronic GVHD.
Discussion
HCT has been effective therapy to prevent neurocognitive decline and ensure long-term survival in selected inherited metabolic storage disorders.7., 10. Benefits stem from enzyme-replete donor cells repopulating various host tissues and adoptively transferring enzyme to nearby enzyme-deficient host cells.14 The neuronal benefits are consequent to the migration of donor-derived cells to the central nervous system of the recipient.10 Patients with α-mannosidosis, including those with the type II
References (18)
- et al.
Clinical manifestations of mannosidosis: a longitudinal study
Am J Med
(1976) - et al.
Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy
Lancet
(2000) - et al.
Quantitative determination of bone marrow transplant engraftment using fluorescent polymerase chain reaction primers for human identity markers
Blood
(1995) - et al.
Bone marrow transplantation for the treatment of alpha-mannosidosis
J Pediatr
(1998) Disorders of glycoprotein degradation: alpha-mannosidosis, beta-mannosidosis, fucosidosis, and sialidosis
- et al.
The clinical course of mannosidosis
Ann Clin Res
(1982) - et al.
Mannosidosis
- et al.
Screening for lysosomal disorders
- et al.
Bone marrow transplantation for globoid cell leukodystrophy, adrenoleukodystrophy, metachromatic leukodystrophy, and Hurler syndrome
Curr Opin Hematol
(1999)
Cited by (61)
Developmental and Inherited Liver Disease
2023, MacSween's Pathology of the Liver, Eighth EditionHearing loss in inherited metabolic disorders: A systematic review
2021, Metabolism: Clinical and ExperimentalCitation Excerpt :Therapy strategies include ERT and bone marrow transplantation. ERT appears to be more appropriate for improving biochemical and functional parameters [78], while bone marrow transplant may permit improved hearing, possibly due the reduction of serous otitis [79]. β-Mannosidosis (OMIM #248510) is an AR lysosomal storage disorder linked to β-mannosidase activity deficiency.
Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis
2020, Molecular Genetics and Metabolism ReportsCitation Excerpt :Treatment options for alpha-mannosidosis are limited. Allogeneic hematopoietic stem cell transplantation (HSCT) has been used to preserve neurocognitive function, improve general status, and prevent early death [10–12], although a better understanding of HSCT timing and regimens as well as impact on outcomes is needed [10,13]. Enzyme replacement therapy (ERT) with a recombinant human alpha-mannosidase (velmanase alfa) is scheduled for clinical development in the US beginning in 2020 and has been approved in the EU for treatment of non-neurological manifestations in individuals with mild to moderate disease.
Developmental and Inherited Liver Disease
2018, MacSween's Pathology of the LiverPersonalized Pharmacoperones for Lysosomal Storage Disorder: Approach for Next-Generation Treatment
2016, Advances in Protein Chemistry and Structural BiologyCitation Excerpt :Thus, produced enzyme will be taken up by mannose-6-phosphate receptors on the cells, endocytosed, and delivered to the lysosome showing the normalized function. LSDs like MPS I, MPS II, MPS III, MPS VI, MPS VII, GLD/Krabbe disease, MLD, Wolman's disease, Mucolipidosis type II (I-cell disease), α-Mannosidosis, Fucosidosis, Niemann–Pick type A and B, Gaucher's disease, ceroid-lipofuscinosis neuronal 3 (CLN3)/Batten disease, Fabry disease, Sandhoff disease, and aspartylglucosaminuria (Grewal et al., 2004; Krivit, 2004; Ringdén et al., 2006) were treated with HSCT and showed some progressive reports. The major drawback in HSCT is its high morbidity, mortality, and graft failure.
Total Body Irradiation
2015, Clinical Radiation Oncology
- ☆
Supplementary data associated with this article can be found at doi:10.1016/j.jpeds.2004.01.025