tacrolimus and Multiple-Endocrine-Neoplasia-Type-1

Patients, in particular recipients of orthotopic liver transplants, receiving the immunosuppressant tacrolimus (FK-506), are at risk for developing central neurotoxic adverse events. We report the occurrence of a tacrolimus-induced peripheral neurotoxic event, i.e. pure motor axonal polyneuropathy of the lower limbs in a 44-year-old woman, 9 days after combined orthotopic liver and pancreas transplantation. She was treated for 5 days with intravenous immunoglobulins. Partial recovery followed over months to years. An overview of all 11 reported FK506-associated polyneuropathies is given.

Topics: Adult; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Liver Transplantation; Magnetic Resonance Imaging; Multiple Endocrine Neoplasia Type 1; Pancreas Transplantation; Pancreatectomy; Polyneuropathies; Tacrolimus

The MEN1 gene is considered to be a tumour suppressor gene and has been localised to a 1-Mb region of 11q13.1. In this study, we report the physical localisation of the 13-kDa FK506 and rapamycin binding protein gene (FKBP2) to the cosmid marker D11S750, which is located inside the MEN1 region of non-recombination. The product of this gene is involved in signal transduction and is thus a candidate cell growth regulator or tumour suppressor gene. Northern studies have revealed that FKBP2 is expressed in those tissues predisposed to hyperplasia in MEN1; however, single-strand conformation polymorphism analysis and direct sequencing of DNAs from affected members of MEN1 kindreds and sporadic tumour DNAs have been performed and no mutations have been found. These studies exclude FKBP2 as a candidate gene for MEN1.

Topics: Base Sequence; Carrier Proteins; Chromosome Mapping; Cosmids; DNA-Binding Proteins; DNA, Neoplasm; Genes, Tumor Suppressor; Genetic Markers; Heat-Shock Proteins; Humans; Molecular Sequence Data; Molecular Weight; Multiple Endocrine Neoplasia Type 1; Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Tacrolimus; Tacrolimus Binding Proteins