Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series
Abstract Background Multiple sulfatase deficiency (MSD) is an exceptionally rare neurodegenerative disorder due to the absence or deficiency of 17 known cellular sulfatases. The activation of all these cellular sulfatases is dependent on the presence of the formylglycine-generating enzyme, which is...
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Nature Portfolio
2025-01-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-024-00703-8 |
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| author | Nishitha R. Pillai Ning Liu Xiyuan Li Xiqi Li Rebecca Ahrens-Nicklas Laura Adang Julie B. Eisengart Grace Bronken Ashish Gupta Troy C. Lund Chester B. Whitley Sarah H. Elsea Paul J. Orchard |
| author_facet | Nishitha R. Pillai Ning Liu Xiyuan Li Xiqi Li Rebecca Ahrens-Nicklas Laura Adang Julie B. Eisengart Grace Bronken Ashish Gupta Troy C. Lund Chester B. Whitley Sarah H. Elsea Paul J. Orchard |
| author_sort | Nishitha R. Pillai |
| collection | DOAJ |
| description | Abstract Background Multiple sulfatase deficiency (MSD) is an exceptionally rare neurodegenerative disorder due to the absence or deficiency of 17 known cellular sulfatases. The activation of all these cellular sulfatases is dependent on the presence of the formylglycine-generating enzyme, which is encoded by the SUMF1 gene. Disease-causing homozygous or compound heterozygous variants in SUMF1 result in MSD. Other than symptomatic treatment, no curative therapy exists as of yet for MSD. Eight out of these 17 sulfatases are primarily localized in the lysosome. Methods Two siblings with attenuated MSD underwent hematopoietic cell transplantation (HCT), evaluating the possibility of lysosomal enzymatic cross-correction from the donor cells. Results There is evidence of correction of currently available biomarkers within 3 months post-HCT. Untargeted metabolomics also shows continued correction of multiple biochemical abnormalities in the post-HCT period. Furthermore, this article also presents the neuropsychological outcomes of these children as well as the results of untargeted metabolomics analysis in this condition. Conclusions These data suggest biochemical benefits post-transplant along with slowing of disease progression. Long-term follow-up is necessary to fully evaluate the therapeutic benefit of HCT in MSD. |
| format | Article |
| id | doaj-art-efee78c1398a4247b58e7088b99cd39c |
| institution | OA Journals |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-efee78c1398a4247b58e7088b99cd39c2025-08-20T02:36:39ZengNature PortfolioCommunications Medicine2730-664X2025-01-01511910.1038/s43856-024-00703-8Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case seriesNishitha R. Pillai0Ning Liu1Xiyuan Li2Xiqi Li3Rebecca Ahrens-Nicklas4Laura Adang5Julie B. Eisengart6Grace Bronken7Ashish Gupta8Troy C. Lund9Chester B. Whitley10Sarah H. Elsea11Paul J. Orchard12Department of Pediatrics, Division of Genetics and Metabolism, University of MinnesotaDepartment of Molecular and Human Genetics, Baylor College of MedicineDepartment of Molecular and Human Genetics, Baylor College of MedicineDepartment of Molecular and Human Genetics, Baylor College of MedicineDepartment of Pediatrics, Division of Human Genetics at Children’s Hospital of PhiladelphiaDepartment of Pediatrics, Division of Neurology at Children’s Hospital of PhiladelphiaDepartment of Pediatrics, Division of Clinical Behavioral Neuroscience, University of MinnesotaM Health, Fairview, MinneapolisDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of MinnesotaDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of MinnesotaDepartment of Pediatrics, Division of Genetics and Metabolism, University of MinnesotaDepartment of Molecular and Human Genetics, Baylor College of MedicineDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of MinnesotaAbstract Background Multiple sulfatase deficiency (MSD) is an exceptionally rare neurodegenerative disorder due to the absence or deficiency of 17 known cellular sulfatases. The activation of all these cellular sulfatases is dependent on the presence of the formylglycine-generating enzyme, which is encoded by the SUMF1 gene. Disease-causing homozygous or compound heterozygous variants in SUMF1 result in MSD. Other than symptomatic treatment, no curative therapy exists as of yet for MSD. Eight out of these 17 sulfatases are primarily localized in the lysosome. Methods Two siblings with attenuated MSD underwent hematopoietic cell transplantation (HCT), evaluating the possibility of lysosomal enzymatic cross-correction from the donor cells. Results There is evidence of correction of currently available biomarkers within 3 months post-HCT. Untargeted metabolomics also shows continued correction of multiple biochemical abnormalities in the post-HCT period. Furthermore, this article also presents the neuropsychological outcomes of these children as well as the results of untargeted metabolomics analysis in this condition. Conclusions These data suggest biochemical benefits post-transplant along with slowing of disease progression. Long-term follow-up is necessary to fully evaluate the therapeutic benefit of HCT in MSD.https://doi.org/10.1038/s43856-024-00703-8 |
| spellingShingle | Nishitha R. Pillai Ning Liu Xiyuan Li Xiqi Li Rebecca Ahrens-Nicklas Laura Adang Julie B. Eisengart Grace Bronken Ashish Gupta Troy C. Lund Chester B. Whitley Sarah H. Elsea Paul J. Orchard Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series Communications Medicine |
| title | Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series |
| title_full | Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series |
| title_fullStr | Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series |
| title_full_unstemmed | Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series |
| title_short | Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series |
| title_sort | bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency a case series |
| url | https://doi.org/10.1038/s43856-024-00703-8 |
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