Abstract
Griscelli syndrome is characterized by partial albinism with variable immunodeficiency. Two different gene loci are responsible for this rare, autosomal recessive disease: the myosin Va gene and the RAB27A gene. As recently reported, only patients with mutations of the RAB27A gene suffer from immunodeficiency and hemophagocytic lymphohistiocytosis. Thus, only patients who suffer from the Griscelli syndrome with mutations of the RAB27A gene should receive BMT/PBSCT, which is the only curative therapy. Due to the risk of early relapse or severe infections, BMT/PBSCT should be carried out as soon as possible; if patients do not have HLA-identical family members, valuable time may be lost by searching for an HLA-identical unrelated donor. We report the first peripheral blood stem cell transplant (PBSCT) with T cell depletion in a 6-month-old girl with Griscelli syndrome, and a deletion of the RAB27A gene. The donor was her phenotypically HLA-identical mother. Conditioning included busulfan, VP16 and cyclophosphamide. The patient was transfused with 15.4 × 106CD34-positive cells/kg and 17.6 × 103 CD3-positive cells/kg recipient weight. Three months after the transplant, a curable lymphoproliferative syndrome occurred. 26 months after the transplant, the patient is doing well with stable mixed chimerism (52% donor cells). Bone Marrow Transplantation (2001) 28, 409–412.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Griscelli C, Durandy A, Guy-Grand D et al. A syndrome associating partial albinism and immunodeficiency Am J Med 1978 65: 691–702
Pastural E, Barrat FJ, Dufourcq-Lagelouse R et al. Griscelli disease maps to chromosome 15q21 and is associated with mutations in the Myosin-Va Gen Nat Genet 1997 16: 289–292
Pastural E, Ersoy F, Yalman N et al. Two genes are responsible for Griscelli syndrome at the same 15q21 locus Genomics 2000 63: 299–306
Stephan JL, Donadieu J, LeDeist F et al. Treatment of hemophagocytic lymphohistiozytosis with antithymocyte globulins, steroids and cyclosporin A Blood 1993 82: 2319–2323
Klein C, Philippe N, LeDeist F et al. Partial albinism with immunodeficiency (Griscelli syndrome) J Pediatr 1994 125: 886–895
Schneider L, Berman R, Shea C et al. Bone marrow transplantation (BMT) for the syndrome of pigmentary dilution and lymphohistiocytosis (Griscelli's syndrome) J Clin Immunol 1990 10: 146–153
Baumeister F, Stachel D, Schuster F et al. Accelerated phase in partial albinism with immunodeficency (Griscelli syndrome): genetics and stem cell transplantation in a 2-month-old girl Eur J Pediatr 2000 159: 74–78
Stachel DK, Schmid I, Schuster F et al. Lymphoproliferative syndrome in an infant after stem cell transplantation: successful therapy with T-lymphocytes and anti-CD20 monoclonal antibodies Med Pediatr Oncol 2000 35: 503–505
Mancini A, Chan L, Paller A . Partial albinism with immunodeficiency: Griscelli syndrome: Report of a case and review of the literature J Am Acad Dermatol 1998 38: 295–300
Ménasché G, Pastural E, Feldmann J et al. Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome Nat Genet 2000 25: 173–176
Lambert J, Onderwater J, Vander Haeghen Y et al. Myosin V colocalizes with melanosomes and subcortical actin bundles not associated with stress fibers in human epidermal melanocytes J Invest Dermatol 1998 111: 835–840
Prekeris R, Terrian DM . Brain myosin V is a synaptic vesicle-associated motor protein: evidence for a Ca2+-dependent interaction with the synaptobrevin–synaptophysin complex J Cell Biol 1997 137: 1589–1601
Hurvitz H, Gillis R, Klaus S et al. A kindred with Griscelli disease: spectrum of neurological involvement Eur J Pediatr 1993 152: 402–405
Stepp SE, Dufourcq-Lagelouse R, LeDeist F et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis Science 1999 286: 1957–1959
Fischer A, Cerf-Bensussan N, Blache S et al. Allogenic bone marrow transplantation for erythrophagocytic lymphohistiocytosis J Pediatr 1986 108: 267–270
Fischer A, Griscelli C, Friedrich W et al. Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European Survey 1968–1985 Lancet 1986 2: 1080–1084
Jabado N, de Graeff-Meeder E, Cavazzana-Calvo M et al. Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors Blood 1997 90: 4743–4748
Acknowledgements
We thank Dr E Pastural and Dr G de Saint Basile for determining the mutations in our patient and her family. This work was supported by the ‘Elterninitiative Intern 3’ Association, Munich.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schuster, F., Stachel, D., Schmid, I. et al. Griscelli syndrome: report of the first peripheral blood stem cell transplant and the role of mutations in the RAB27A gene as an indication for BMT. Bone Marrow Transplant 28, 409–412 (2001). https://doi.org/10.1038/sj.bmt.1703114
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1703114
Keywords
This article is cited by
-
Hematopoietic stem cell transplantation in children with Griscelli syndrome type 2: a single-center report on 35 patients
Bone Marrow Transplantation (2020)
-
Griscelli Syndrome with Fibronodular Sclerodermatous Chronic Graft Versus Host Disease
Indian Journal of Hematology and Blood Transfusion (2018)
-
Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism
Orphanet Journal of Rare Diseases (2013)
-
Hematopoietic SCT in children with Griscelli syndrome: a single-center experience
Bone Marrow Transplantation (2010)
-
Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders
European Journal of Pediatrics (2008)