Proposal for updating the pseudoxanthoma elasticum classification system and a review of the clinical findings.

Pseudoxanthoma elasticum (PXE) is a systemic disorder affecting elastic tissues most markedly in skin, retina, and blood vessels. It is caused by mutations in the ABCC6 gene and is transmitted in an autosomal recessive fashion. In 1994 a new classification system for PXE was published as the result of a consensus conference. Since then the ABCC6 gene has been discovered. We propose that there is a need for a classification system incorporating all relevant systemic symptoms and signs, based on standardized clinical, histological, and molecular biological examination techniques. We re-evaluated the histopathologic PXE signs and propose a classification system with unambiguous criteria leading to a consistent diagnosis of definitive, probable, or possible PXE world-wide. We put this proposed classification forward to encourage further debate on the diagnosis of this multi-organ disorder.

[Increased haemoglobin A2 levels in pseudoxanthoma elasticum]. / Augmentation de l'hémoglobine A2 au cours du pseudoxanthome élastique.

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. PATIENTS AND 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. DISCUSSION: 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.

Descubriendo el pseudoxantoma elástico / Discovering the elasticum pseudoxanthoma

Enfermedad hereditaria rara, el pseudoxantoma elástico es un trastorno genético del tejido conectivo, que se caracteriza por fragmentación de las fibras elásticas y posterior calcificación de éstas afectando dermis, vasos sanguíneos y la membrana de Bruch de retina. El patrón de herencia es muy variable, lo que hace posible que esta enfermedad pueda estar subdiagnosticada. La escasa incidencia de esta patología justifica la presentación de dos casos que tuvieron solamente manifestaciones cutáneas.

Hereditary disease does not frequent pseudoxanthoma elastic; is a genetic upheaval of the conective weave, that characterizes by fragmentation of elastic fibers and later calcification of these, affecting dermis, blood vessels and membrane of Bruch of retina. The inheritance pattern is very variable which causes that disease; can be subdiagnosed. The litlle incidence of this pathology, causes that in our professional experience we have been able to diagnose two cases in which the manifestations were cutaneous.

Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a heritable disease characterized by dermal, ocular, and vascular lesions that result from degeneration of the elastic fibers. Recently, the ATP-binding cassette subfamily C member 6 (ABCC6) gene has been demonstrated to be responsible for PXE, and 43 mutations have been identified to date. However, it is still unknown now mutations in the ABCCC6 gene can lead to manifestations of PXE.

[Pseudoxanthoma elasticum in pregnancy]. / Association pseudoxanthome élastique et grossesse.

Pseudoxanthoma elasticum (PXE) is a rare form of congenital dystrophy of the elastic tissue, which is characterized by cutaneous, ocular and vascular impact. There are four clinical forms which correspond to 4 different genetic types (I or II, dominant or recessive). The vascular damage caused by the illness general limits the obstetric prognosis. Under our observation, the pregnancy of a woman 34 years of age suffering from type II PXE proceeded without problem.

[Systemic cutis laxa-like pseudoxanthoma elasticum]. / Systemisches Cutis-laxa-artiges Pseudoxanthoma elasticum.

According to Pope the pseudoxanthoma elasticum (PXE) can be divided into four types using clinical genetical criteria. In contrast to the classical form the recessive type II is not only characterized by a wrinkeled appearance and laxity of the skin, furthermore there are no clinical symptoms indicating visceral disease. We report two patients with cutis laxa-like skin. In addition the patients suffered from pathological changes of the eye. In one of them an alteration of the peripher vascular system could be observed.