Bone marrow transplantation (BMT) has been used for a wide variety of
lysosomal storage diseases with encouraging results. We report a 3-year 5-month-old girl with
Niemann-Pick type C disease (NPC) who received an allogeneic BMT. The patient presented with repeated lower
respiratory tract infections, hepatosplenomegaly,
failure to thrive, and developmental delay. Chest computed tomography (CT) revealed diffuse interstitial lung infiltration. Bone marrow and liver biopsies revealed abundant
lipid-filled foamy macrophages. Skin fibroblast
sphingomyelinase assay revealed partial deficiency. The ability of her skin fibroblasts to esterify
cholesterol was very low, and the cells stained brightly for free
cholesterol. She received BMT from a healthy HLA-identical male sibling donor at the age of 2 year 6 months. Full engraftment was evidenced by repeated bone marrow sex chromosome studies. Regression of the hepatosplenomegaly, markedly reduced foamy macrophage infiltration in bone marrow, and decreased interstitial lung infiltration was noted 6 months after BMT. Her neurological status, however, deteriorated. Follow-up magnetic resonance image (MRI) revealed progressive, diffuse brain
atrophy. We conclude that resolution occurred in the liver, spleen, bone marrow and lung following successful engraftment. Such a response is remarkable since the underlying problem involves a membrane receptor for
cholesterol. This positive response might be due to replacement of the monocyte-phagocytic system or it may imply the existence of cross-correction in the NPC membrane receptor defect by BMT approach. Since BMT did not halt the neurological deterioration, it is unlikely to be an adequate treatment for NPC.