Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series

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

doi:10.1038/s43856-024-00703-8

Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series

Commun Med (Lond). 2025 Jan 9;5(1):12. doi: 10.1038/s43856-024-00703-8.

Authors

Nishitha R Pillai¹, Ning Liu^{2

3}, Xiyuan Li^{2

3}, Xiqi Li², Rebecca Ahrens-Nicklas⁴, Laura Adang⁵, Julie B Eisengart⁶, Grace Bronken⁷, Ashish Gupta⁸, Troy C Lund⁸, Chester B Whitley⁹, Sarah H Elsea^{2

3}, Paul J Orchard⁸

Affiliations

¹ Department of Pediatrics, Division of Genetics and Metabolism, University of Minnesota, Minneapolis, MN, USA. [email protected].
² Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
³ Baylor Genetics Laboratories, Houston, TX, USA.
⁴ Department of Pediatrics, Division of Human Genetics at Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁵ Department of Pediatrics, Division of Neurology at Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶ Department of Pediatrics, Division of Clinical Behavioral Neuroscience, University of Minnesota, Minneapolis, MN, USA.
⁷ M Health, Fairview, Minneapolis, Minnesota, MN, USA.
⁸ Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA.
⁹ Department of Pediatrics, Division of Genetics and Metabolism, University of Minnesota, Minneapolis, MN, USA.

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.

Plain language summary

Multiple sulfatase deficiency (MSD) is a genetic disorder in which body is unable to produce certain enzymes which are a type of protein. MSD affects multiple body systems, primarily the brain. The current treatments available are catered toward easing the symptoms and cannot cure the disease. In this study, two siblings with a mild form of MSD received bone marrow transplantation (HCT) that replaced their bone marrow with stem cells containing the healthy version of the gene responsible for MSD. The children were monitored for two years, during which time the siblings continued to produce the enzymes that are normally absent in MSD and did not have mental or behavioral deterioration. This study suggests that HCT might help slow the progress of MSD and be an improved treatment. However, further and longer-term studies are required to investigate this further.