Evidence of oxidative stress in familial amyloidotic polyneuropathy type 1.
OBJECTIVE
To evaluate the oxidative state in patients with familial amyloidotic polyneuropathy type 1 (FAP1).


METHODS
From 3 unrelated families, patients with FAP1 carrying a transthyretin Met-30 mutation were studied. The diagnosis was confirmed by genetic analysis. Eleven of 21 patients carried the mutation; all were symptomatic and were clinically assessed using a clinical score. All of the patients were evaluated for copper-zinc superoxide dismutase type 1 activity in red blood cells using spectrophotometry. Plasma total reactive antioxidant potential was studied using a chemiluminescent method. The results were compared with those obtained from an age-matched control group.


METHODS
A public and academic multidisciplinary research clinic.


RESULTS
Six of the 11 FAP1-positive patients disclosed superoxide dismutase type 1 activity values greater than 55 U/mg of protein (upper control limit), whereas 9 of 10 patients in whom total reactive antioxidant potential was measured had values below the lower limit of the control group. No relationship was found between the levels of superoxide dismutase type 1 activity and the severity of the clinical involvement.


CONCLUSIONS
Oxidative stress may be part of the mechanisms leading to tissue damage in patients with FAP1. The lack of correlation between the laboratory findings and the severity of clinical involvement may signal that oxidative processes are at work throughout the natural history of the disease.
Fiszman
Mónica L
ML
Instituto de Investigaciones Farmacológicas-CONICET.
Di Egidio
Marianna
M
Ricart
Karina C
KC
Repetto
Marisa G
MG
Borodinsky
Laura N
LN
Llesuy
Susana F
SF
Saizar
Roberto D
RD
Trigo
Pedro L
PL
Riedstra
Symon
S
Costa
Paulo P
PP
Villa
Andrés M
AM
Katz
Nestor
N
Lendoire
Javier C
JC
Sica
Roberto E P
RE
D028227:Amyloid Neuropathies, Familial / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D000975:Antioxidants / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D003488:Cyanogen Bromide / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology*; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D008715:Methionine / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011228:Prealbumin / Q000235:genetics; D017382:Reactive Oxygen Species / Q000097:blood*; D013482:Superoxide Dismutase / Q000097:blood*; D000072105:Superoxide Dismutase-1; D014633:Valine / Q000235:genetics; D015032:Zinc / Q000378:metabolism
D000975:Antioxidants; D011228:Prealbumin; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D003300:Copper; D008715:Methionine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014633:Valine; D015032:Zinc; D003488:Cyanogen Bromide