BMT for CGL – pro
This is a storage disease, one of a relatively rare group of disorders in which there is a deficiency of a particular enzyme necessary for normal metabolic processes within the body. The result is an accumulation in cells (“storage”) of whatever product the enzyme normally acts upon. Typically, animals with a storage disease are normal at birth, fail to grow as rapidly as littermates, and at a consistent age, develop progressive signs of a disorder of the nervous system which will ultimately be fatal.
In globoid cell leukodystrophy (GCL), the lack of the enzyme ß-galactocerebrosidase results in an accumulation of galactocerebroside, a component of myelin. This disrupts the cells that normally produce myelin, a fatty substance that coats nerve cells, serves as an electrical insulator and is crucial to the normal conduction of nerve impulses. The progressive loss of myelin in the white matter tracts of the nervous system (brain, spinal cord and/or peripheral nerves) causes a variety of clinical signs such as lack of coordination, tremors, and weakness.
With appropriate timing and use of allogeneic stem cells, GCL can be effectively treated in late onset cases with normalization of CSF protein, stabilization of the neurologic examination, neuropsychologic function, and the extent of demyelination on MRI. However, to date, Krabbe disease, if diagnosed antenatally, can only be ameliorated if HCT is performed in the neonatal period.
C Peters et al, Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines BMKT, February (2) 2003, Volume 31, Number 4, Pages 229-239
Kurtzberg J, Richards K, Wenger D et al.. Correction of Krabbe disease with neonatal hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2002; 8: 97 (Abstr. 130).
Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med 1998; 338: 1119-1126.