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Five-Year Follow-Up of Two Siblings with Aspartylglucosaminuria Undergoing Allogeneic Stem-Cell Transplantation from Unrelated Donors

Malm, Gunilla1,5; Månsson, Jan-Eric2; Winiarski, Jacek1; Mosskin, Mikael3; Ringdén, Olle4

Clinical Transplantation

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.

Conclusion. 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.

1 Department of Pediatrics, Karolinska University Hospital, Huddinge Hospital, Stockholm, Sweden.

2 Institute of Clinical Neuroscience, Section of experimental neuroscience, Sahlgren’s University Hospital, Mölndal.

3 Department of Neuroradiology, Karolinska Hospital, Stockholm, Sweden.

4 Department of Clinical Immunology and Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge Hospital Stockholm, Sweden.

5 Address correspondence to: Dr. G. Malm, Department of Paediatrics, Karolinska University Hospital, Huddinge Hospital, S-14186, Stockholm, Sweden. E-mail: gunilla.malm@hs.se.

This study was supported by grants from the Swedish Cancer Society (0070-B02–16XAC), The Children’s Cancer Foundation (2000/067, 2002/074), The Swedish Research Council (K2003–32X-05971–23A), The Cancer Society in Stockholm (02:181), The Tobias Foundation, and the Karolinska Institute.

Received 9 October 2003. Accepted 16 February 2004.

© 2004 Lippincott Williams & Wilkins, Inc.