The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance.
BACKGROUND
Despite great progress in understanding the mechanisms underlying genetic hemochromatosis, data on the prevalence and the penetrance of the disorder are conflicting.


METHODS
A registry of patients with genetic hemochromatosis was established in the South of France and a regional health network was developed to allow the inclusion of all the diagnosed patients. C282Y homozygous patients classified in stages 2 (biological iron overload), 3 and 4 (clinical manifestations of iron overload, stage 4 being the more severe) according to the classification of the French National Authority for Health were included in the registry over a 6-year period.


RESULTS
A total of 352 symptomatic C282Y homozygotes were identified, resulting in a total prevalence of 1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per 10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1% in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in subjects between 50 and 54 years old. Among 249 patients with complete records, 24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4. There was a higher proportion of males, and excessive alcohol intake was more prevalent in stage 4 than in stages 2 and 3 combined.


CONCLUSIONS
A French Mediterranean regional hemochromatosis registry with strict inclusion criteria is a useful tool for characterizing the history of this disease, particularly for the most severely affected patients, as defined by the disease severity classification. The total prevalence of symptomatic C282Y homozygotes in the region was found to be low. However, clinical penetrance (stages 3 and 4) was not negligible.
CHU of Montpellier Laboratory of Hematology, Hôpital Saint Eloi, Avenue Augustin Fliche, 34295 Montpellier Cedex 5, France. p-martinez@chu-montpellier.fr
Patricia
P
Aguilar-Martinez
Michael
M
Bismuth
François
F
Blanc
Pierre
P
Blanc
Severine
S
Cunat
Olivier
O
Dereure
Pierre
P
Dujols
Muriel
M
Giansily-Blaizot
Christian
C
Jorgensen
Amadou
A
Konate
Dominique
D
Larrey
Alain
A
Le Quellec
Thibault
T
Mura
Isabelle
I
Raingeard
Jeanne
J
Ramos
Eric
E
Renard
Florence
F
Rousseau
Jean-François
JF
Schved
Marie-Christine
MC
Picot
D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019683:Penetrance; D012042:Registries; D044465:White People