NDLI: Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome

Content Provider	Springer Nature : BioMed Central
Author	Jester, Sandra Larsson, Julia Eklund, Erik A Papadopoulou, Domniki Månsson, Jan-Eric Békássy, Albert N Turkiewicz, Dominik Toporski, Jacek Øra, Ingrid
Abstract	Background Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive progressive multiorgan disorder due to mutation in the gene encoding the enzyme Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is preferred to hematopoietic stem cell transplantation (SCT) due to the treatment-related risks of the latter. However, ERT constitutes an expensive life-long treatment. Increased experience and safety of SCT-procedures in recent years suggest that SCT should be further explored as a treatment option. This is the first report on haploidentical SCT in patients with MPS VI. The primary objective was to assess the treatment safety and clinical and biochemical outcome. Patients and methods Two siblings diagnosed with MPS VI at 10 months of age and at birth with genotype p.C192R, reported as mild to intermediate phenotype, underwent unrelated umbilical cord blood transplantation pre-symptomatic. Due to graft failure, both patients were urgently re-transplantated with haploidentical SCT with the father as donor. Continuous clinical and biochemical status was monitored and concluded 3.8 and 4.6 years after the haploidentical SCT. Results Haploidentical SCT resulted in prompt and sustained engraftment. Complete donor chimerism was achieved in both patients, apart from mixed B cells chimerism in patient 2. ARSB activity in leukocytes post transplant increased from 0.0 to 19.0 μkat/kg protein (patient 1) and from 3.6 to 17.9 μkat/kg protein (patient 2) (ref. 17–40). Total urinary GAG normalized in both patients, although patient 2’s values slightly exceed normal range since 6 months. However, dermatan sulfaturia was substantially normalized since 16 months and 12 months post-SCT, respectively. Height was -1.85 SD and -1.27 SD at follow-up. Patient 1 had impaired visual acuity and discrete hepatomegaly. Patient 2 had elevated intraocular pressure and X-ray revealed steep acetabular angles and slightly flattened lumbar vertebrae. Conclusion This study demonstrates that young children with MPS VI tolerate haploidentical SCT. Normalization of enzyme production and dermatan sulfaturia indicates correction of the inborn error of metabolism and coincide with no obvious symptoms of progressive MPS VI up to 4.6 years post-SCT.
Related Links	https://ojrd.biomedcentral.com/counter/pdf/10.1186/1750-1172-8-134.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	17501172
DOI	10.1186/1750-1172-8-134
Journal	Orphanet Journal of Rare Diseases
Issue Number	1
Volume Number	8
Language	English
Publisher	BioMed Central
Publisher Date	2013-09-05
Access Restriction	Open
Subject Keyword	Medicine Public Health Pharmacology Toxicology Human Genetics Mucopolysaccharidosis VI Haploidentical stem cell transplantation Clinical outcome Medicine/Public Health Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Pharmacology (medical) Genetics (clinical)
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.9/2023

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