[Increased haemoglobin A2 levels in pseudoxanthoma elasticum].
BACKGROUND
Pseudoxanthoma elasticum (PXE) is normally associated with mutations in the ABCC6 gene. A PXE phenotype without mutations in ABCC6 has been described in Greek and Italian patients presenting with beta thalassemia. We attempted to determine the incidence of beta thalassemia in a cohort of French patients with PXE.


METHODS
Fifty patients with PXE were included in the study. Laboratory examinations comprised hemoglobin electrophoresis, ABCC6 gene study and in some studies: mutation analysis, beta-globin gene.


RESULTS
No cases of beta thalassemia were diagnosed in this cohort of French patients with PXE. However, 20% of the latter exhibited a significant but isolated (i.e. without microcytic anemia) increase of hemoglobin A2 (HbA2). Statistical comparisons showed no difference in terms of geographical origin or severity of PXE between patients with high levels of HbA2 and those with normal levels of HbA2 other than the extent of cutaneous involvement. Study of the beta-globin gene displayed mutations only in the two patients with the highest recorded levels of HbA2. ABCC6 + beta-globin digenism was ruled out of the pathogenesis of PXE.


CONCLUSIONS
The PXE phenotype seen in some patients with beta thalassemia appears to be associated with epigenetic modification of ABCC6 transcription and depends specifically on the beta globin locus. Isolated increase in HbA2 is probably a laboratory marker for PXE. Here again, a functional epigenetic reaction between ABCC6 and the beta-globin locus was suspected. However, these reciprocal interactions are clearly unequal since the change in ABCC6 transcription occurring during the course of beta thalassaemia is responsible for a PXE phenotype while increased HbA2 during the course of PXE has no clinical consequences.
Martin
L
L
Consultation Multidisciplinaire PXE, CHR d'Orléans, Cedex, France. ludovic.martin@chr-orleans.fr
Pissard
S
S
Blanc
P
P
Chassaing
N
N
Legac
E
E
Briault
S
S
Le Bert
M
M
Le Saux
O
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D044127:Epigenesis, Genetic / Q000235:genetics; D004911:Erythrocyte Volume; D005260:Female; D005914:Globins / Q000032:analysis / Q000235:genetics; D006443:Hemoglobin A2 / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011561:Pseudoxanthoma Elasticum / Q000097:blood* / Q000145:classification / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D017086:beta-Thalassemia / Q000097:blood
D005914:Globins; D006443:Hemoglobin A2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human