Five-year follow-up of two siblings with aspartylglucosaminuria undergoing allogeneic stem-cell transplantation from unrelated donors.
BACKGROUND
Aspartylglucosaminuria is a rare, inherited lysosomal disease characterized by a slowly progressive mental retardation and coarse facial and body features. With the intent to provide the deficient enzyme aspartylglucosaminidase, allogeneic stem-cell transplantation (ASCT) has been attempted. Only a few cases of transplants have been reported.


METHODS
Two siblings with aspartylglucosaminuria underwent allogeneic bone marrow transplants using unrelated human leukocyte antigen-A, -B, and DR identical donors at ages 10 years 5 months and 5 years 10 months, respectively. They were followed during 5 years with biochemical, neuroradiologic, neuropsychologic, and clinical investigations.


RESULTS
During 5 years follow-up, no neuropsychologic or clinical deterioration was noted in the children. A stable expression of aspartylglucosaminidase was found during the whole follow-up period. The spinal fluid concentration of Tau-protein, a marker of neuronal and axonal degeneration and damage, peaked at approximately 12 months after bone-marrow transplantation and then declined to almost normal levels after 5 years. By magnetic resonance imaging (MRI), an improvement of myelination in the youngest sibling and an arrest of demyelination in the older one were observed.


CONCLUSIONS
The importance of long-term follow-up of children after ASCT in this rare, very slowly progressive lysosomal disease must be emphasized. We report that none of the children had lost any capabilities since the transplantation; moreover, an improvement is shown in biochemical markers and MRI white-matter signals, suggesting a beneficial effect.
Malm
Gunilla
G
Department of Pediatrics, Karolinska University Hospital, Huddinge Hospital, Stockholm, Sweden. gunilla.malm@hs.se
Månsson
Jan-Eric
JE
Winiarski
Jacek
J
Mosskin
Mikael
M
Ringdén
Olle
O
D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000652:urine*; D000592:Amino Acid Metabolism, Inborn Errors / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008607:Intellectual Disability; D008297:Male; D035781:Siblings; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data*; D014184:Transplantation, Homologous / Q000379:methods*
C000009:N-acetylglucosaminylasparagine; D000117:Acetylglucosamine