Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick disease type A.

Liver homotransplantation was attempted as replacement therapy in a 2-year-old patient with near total absence of sphingomyelinase activity of Niemann-Pick disease type A. Satisfactory function of the graft was observed until the death of the recipient from respiratory complication 2 years after transplantation. The clinical stigmata of the disease became less severe during the first 6 months after transplantation, with no further improvement thereafter. Sphingomyelinase activity was restored to near normal levels in serum, was present in cerebrospinal fluid and was maintained in the graft at normal or supranormal levels. No accumulation of sphingomyelin was observed in the transplanted organ as evaluated by histopathological and chromatographic studies. These findings support the interest of organ transplantation for long-term enzyme replacement in Niemann-Pick disease type A and similar lysosomal deficiencies.