Pseudoxanthoma elasticum: diagnostic features, classification and treatment options

Abstract

Introduction Pseudoxanthoma elasticum (PXE), a multisystem orphan disease, clinically affects the skin, the eyes, and the cardiovascular system with considerable morbidity and mortality. The clinical manifestations reflect the underlying pathology consisting of ectopic mineralization of peripheral connective tissues. Areas Covered The diagnostic criteria of PXE include characteristic clinical findings, together with histopathology of accumulation of pleiomorphic elastic structures in the dermis with progressive mineralization, and the presence of mutations in the ABCC6 gene. PXE-like cutaneous changes can also be encountered in other ectopic mineralization disorders, including generalized arterial calcification of infancy (GACI) caused by mutations in the ENPP1 gene. In some cases, overlapping clinical features of PXE/GACI, associated with mutations either in ABCC6 or ENPP1, have been noted. PXE demonstrates considerable inter- and intrafamilial heterogeneity, and consequently, accurate diagnosis is required for appropriate classification with prognostic implications. There is no effective and specific treatment for the systemic manifestations of PXE, but effective therapies to counteract the ocular complications are in current clinical use. Expert Opinion A number of observations in the murine model, the Abcc6−/− mouse, have indicated that the mineral composition of diet, particularly the magnesium content, can influence the severity of the mineralization phenotype. These observations suggest that appropriate dietary interventions, coupled with lifestyle modifications, including smoking cessation, might alleviate the symptoms and improve the quality of life of individuals affected with this, currently intractable, orphan disease.

Stabilization of Nucleotide Binding Domain Dimers Rescues ABCC6 Mutants Associated with Pseudoxanthoma Elasticum

“…Recent work suggests that a loss of circulating pyrophosphates, resulting from altered nucleotide secretion and conversion by nucleotide pyrophosphatases in the circulatory system, is associated with ectopic mineralization (5,6). At present, only symptomatic treatments exist for PXE (4,7).…”

Vitamin K reduces hypermineralisation in zebrafish models of PXE and GACI

“…Pseudoxanthoma elasticum [PXE; Online Mendelian Inheritance in Man (OMIM) #264800] is a congenital disorder which causes ectopic mineralisation of the eyes, skin and arterial walls, and, in most cases, is associated with mutations in the ABCC6 gene (Bergen et al, 2000;Chassaing et al, 2005;Uitto et al, 2014). The closely related disease generalised arterial calcification of infancy (GACI; OMIM #208000) is characterised by severe vascular mineralisation that is usually lethal in the neonatal period (Cheng et al, 2005).…”

Carotid strain measurement in patients with pseudoxanthoma elasticum – Hint for a different pathomechanism?

“…44 patients had a clinical or a combined clinical and genetical evidence of PXE. The clinical evidence consists of characteristic skin lesions and typical eye and retina changes, whereas the combined evidence implies a genetical evidence of a biallelic loss of function mutation in the ABCC6 gene, assessed in the Institute for Laboratory and Transfusion Medicine at the Heart and Diabetes Centre Bad Oeyenhausen and at least one clinical sign as described above (14).…”

“…Other characteristic signs are ophthalmologic alterations like angoid streaks or retinal pigment epithelium atrophy and cardiovascular manifestations such as a high prevalence of peripheral artery disease (PAD), intermittent claudication or chronic vascular occlusions which are mostly localized in the lower limb specially the femoral arteries (13)(14)(15). Atherosclerosis and PAD are associated with changes in vascular elasticity as observed in non-PXE patients (16).…”