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Previous Volume 338:1119-1127 April 16, 1998 Number 16 Next

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ABSTRACT

Background Globoid-cell leukodystrophy is caused by a deficiency of galactocerebrosidase, which results in progressive central nervous system deterioration. We investigated whether allogeneic hematopoietic stem-cell transplantation can provide a source of leukocyte galactocerebrosidase and thereby prevent the decline of central nervous system function in patients with the disease.

Methods Five children with globoid-cell leukodystrophy (one with the infantile type and four with late-onset disease) were treated with allogeneic hematopoietic stem-cell transplantation. Measurement of leukocyte galactocerebrosidase levels, neurologic examinations, neuropsychological tests, magnetic resonance imaging of the central nervous system, cerebrospinal fluid protein assays, and neurophysiologic measurements were performed before and after transplantation, with follow-up ranging from one to nine years.

Results Engraftment of donor-derived hematopoietic cells occurred in all patients and was followed by restoration of normal leukocyte galactocerebrosidase levels. In the four patients with late-onset disease, the central nervous system deterioration was reversed, and in the patient with the infantile form of the disease, signs and symptoms have not appeared. Magnetic resonance imaging showed a decrease in signal intensity in the three patients with late-onset disease who were assessed both before and after transplantation. Abnormalities in cerebrospinal fluid total protein levels were corrected in three patients with late-onset disease and substantially reduced in the patient with the infantile form.

Conclusions Central nervous system manifestations of globoid-cell leukodystrophy can be reversed by allogeneic hematopoietic stem-cell transplantation.

Source Information

From the Departments of Pediatrics (W.K., C.P., J.E.W.), Neurology (E.G.S., L.A.L.), Therapeutic Radiology (K.D.), and Radiology (D.J.L.), University of Minnesota School of Medicine, Minneapolis; the Université Catholique de Louvain, Brussels, Belgium (G.C.); Duke University School of Medicine, Durham, N.C. (J.K.); Jefferson Medical College, Philadelphia (D.A.W.); New York University School of Medicine, New York (E.H.K.); and INSERM Unité 189, Lyon-Sud School of Medicine, Lyons, France (M.T.V.).

Address reprint requests to Dr. Krivit at the University of Minnesota Hospitals and Clinics, Box 477, Rm. D-548, Mayo Bldg., 420 Delaware St., S.E., Minneapolis, MN 55455.

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