Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the ferritin light polypeptide gene

J Neuropathol Exp Neurol. 2004 Apr;63(4):363-80. doi: 10.1093/jnen/63.4.363.


Abnormal accumulation of ferritin was found to be associated with an autosomal dominant slowly progressing neurodegenerative disease clinically characterized by tremor, cerebellar ataxia, parkinsonism and pyramidal signs, behavioral disturbances, and cognitive decline. These symptoms may appear sequentially over a period of 4 decades. Pathologically, intranuclear and intracytoplasmic bodies were found in glia and subsets of neurons in the central nervous system as well as in extraneural tissue. Biochemical analyses of these bodies isolated from the striatum and cerebellar cortex revealed that ferritin light polypeptide (FTL) and ferritin heavy polypeptide (FTH1) were the main constituents. Molecular genetic studies revealed a 2-bp insertion mutation in exon 4 of the FTL gene. The resulting mutant polypeptide is predicted to have a carboxy terminus that is altered in amino-acid sequence and length. In tissue sections, the bodies were immunolabeled by anti-ferritin and anti-ubiquitin antibodies and were stained by Perls' method for ferric iron. Synthetic peptides homologous to the altered and wild-type carboxy termini were used to raise polyclonal antibodies. These novel antibodies as well as an antibody recognizing FTH1 immunolabeled the bodies. This study of this disorder has provided additional knowledge and insights in the growing area of ferritin-related neurodegeneration.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Western
  • Brain / metabolism
  • Brain / pathology*
  • DNA Mutational Analysis
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Ferritins / genetics*
  • Ferritins / metabolism*
  • Genes, Dominant
  • Humans
  • Immunohistochemistry
  • Inclusion Bodies / chemistry
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / ultrastructure
  • Magnetic Resonance Imaging
  • Microscopy, Electron
  • Molecular Sequence Data
  • Mutation
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology*
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neuroglia / ultrastructure
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / ultrastructure
  • Pedigree
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Protein Subunits
  • Ferritins

Associated data

  • GENBANK/AC027228
  • GENBANK/AF261088
  • GENBANK/AY466472
  • GENBANK/M14211
  • GENBANK/M14212
  • GENBANK/M58511
  • GENBANK/X03742
  • GENBANK/X03743
  • RefSeq/NM_002197