Pseudoxanthoma elasticum

Dominique P Germain

doi:10.1186/s13023-017-0639-8

Abstract

Pseudoxanthoma elasticum (PXE) is a genetic metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. The lack of functional ABCC6 protein leads to ectopic mineralization that is most apparent in the elastic tissues of the skin, eyes and blood vessels. The clinical prevalence of PXE has been estimated at between 1 per 100,000 and 1 per 25,000, with slight female predominance. The first clinical sign of PXE is almost always small yellow papules on the nape and sides of the neck and in flexural areas. The papules coalesce, and the skin becomes loose and wrinkled. The mid-dermal elastic fibers are short, fragmented, clumped and calcified. Dystrophic calcification of Bruch’s membrane, revealed by angioid streaks, may trigger choroidal neovascularization and, ultimately, loss of central vision and blindness in late-stage disease. Lesions in small and medium-sized artery walls may result in intermittent claudication and peripheral artery disease. Cardiac complications (myocardial infarction, angina pectoris) are thought to be relatively rare but merit thorough investigation. Ischemic strokes have been reported. PXE is a metabolic disease in which circulating levels of an anti-mineralization factor are low. There is good evidence to suggest that the factor is inorganic pyrophosphate (PPi), and that the circulating low levels of PPi and decreased PPi/Pi ratio result from the lack of ATP release by hepatocytes harboring the mutant ABCC6 protein. However, the substrate(s) bound, transported or modulated by the ABCC6 protein remain unknown. More than 300 sequence variants of the ABCC6 gene have been identified. There is no cure for PXE; the main symptomatic treatments are vascular endothelial growth factor inhibitor therapy (for ophthalmic manifestations), lifestyle, lipid-lowering and dietary measures (for reducing vascular risk factors), and vascular surgery (for severe cardiovascular manifestations). Future treatment options may include gene therapy/editing and pharmacologic chaperone therapy.

Highlights

Disease name and synonyms Pseudoxanthoma elasticum (PXE); OMIM #264800Grönblad-Strandberg syndrome ICD-10: Q82.8; ORPHA #758Definition The term “pseudoxanthoma elasticum” was coined by the French dermatologist Ferdinand-Jean Darier in 1896 [1], by reference to the yellowish tone of skin features and the lax aspect of the skin at flexural surfaces
Β-thalassemia and sickle cell anemia As mentioned above, skin manifestations resembling those seen in PXE and angioid streaks have been observed in individuals with β-thalassemia and sickle cell disease who clearly lack ABCC6 gene mutations [89, 90]
PXE is associated with a risk of blindness, decreased quality of life and peripheral vascular compromise

Summary

Introduction

Disease name and synonyms Pseudoxanthoma elasticum (PXE); OMIM #264800Grönblad-Strandberg syndrome ICD-10: Q82.8; ORPHA #758Definition The term “pseudoxanthoma elasticum” was coined by the French dermatologist Ferdinand-Jean Darier in 1896 [1], by reference to the yellowish tone of skin features (seen in true cases of xanthoma) and the lax aspect of the skin at flexural surfaces. It has been suggested that heterozygous carriers of ABCC6 mutations (estimated frequency in the general population: up to 1 in 80) have an increased risk of cardiovascular calcification and premature coronary artery disease [15, 43]. As in any autosomal recessive disease, it is generally accepted that heterozygous carriers of a mutation in one ABCC6 allele do not develop PXE [59, 60].

Results

Conclusion