Neuroferritinopathy: a window on the role of iron in neurodegeneration.
Neuroferritinopathy is a recently recognised genetic disease resulting in a dominantly inherited movement disorder. The condition was mapped by linkage analysis to chromosome 19q13.3 and found to be due to a single adenine insertion in the ferritin light chain (FTL) gene at position 460-461 which is predicted to alter the C terminus of the FTL polypeptide. Clinical features of neuroferritinopathy are highly variable, with chorea, dystonia, and Parkinsonian features predominating in different affected individuals. The most consistent feature is a dystonic dysarthria. Symptoms and abnormal physical signs appear to be restricted to the nervous system and onset is typically in the fourth to sixth decades. Low serum ferritin also characterises this condition. Brain MR imaging of affected patients demonstrates iron deposition in the basal ganglia, progressing over years to cystic degeneration, and brain histochemistry shows abnormal aggregates of ferritin and iron. Now that the molecular basis of the condition is known, therapeutic interventions to reduce or reverse brain iron deposition are being evaluated. This rare disease provides evidence of a central role for iron metabolism in neurodegenerative disorders.
Crompton
Douglas E
DE
Institute of Human Genetics, International Centre for Life, Newcastle upon Tyne NE1 3BZ, United Kingdom.
Chinnery
Patrick F
PF
Fey
Constanze
C
Curtis
Andrew R J
AR
Morris
Christopher M
CM
Kierstan
Jo
J
Burt
Alistair
A
Young
Fergus
F
Coulthard
Alan
A
Curtis
Ann
A
Ince
Paul G
PG
Bates
David
D
Jackson
Margaret J
MJ
Burn
John
J
D000595:Amino Acid Sequence; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000378:metabolism*; D010375:Pedigree; D011859:Radiography
D005293:Ferritins; D007501:Iron