Niemann-Pick disease type C (a cellular cholesterol lipidosis) treated by bone marrow transplantation

Bone marrow transplantation (BMT) has been used for a wide variety of lysos omal 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 com puted 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 a bility of her skin fibroblasts to esterify cholesterol was very low, and th e cells stained brightly for free cholesterol, She received BMT from a heal thy HLA-identical male sibling donor at the age of 2 year 6 months. Full en graftment was evidenced by repeated bone marrow sex chromosome studies. Reg ression of the hepatosplenomegaly, markedly reduced foamy macrophage infilt ration in bone marrow, and decreased interstitial lung infiltration was not ed 6 months after BMT, Her neurological status, however, deteriorated. Foll ow-up magnetic resonance image (MRI) revealed progressive, diffuse brain at rophy. We conclude that resolution occurred in the liver, spleen, bone marr ow 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-phagocy tic system or it may imply the existence of cross-correction in the NPC mem brane receptor defect by BMT approach. Since BMT did not halt the neurologi cal deterioraton, it is unlikely to be an adequate treatment for NPC.