Current researchPseudoxanthoma elasticum: a clinical, histopathological, and molecular update
Section snippets
The skin and mucosal membranes
Skin lesions are frequently seen in PXE patients and were initially described in 1881 by Rigal110 and in 1896 by Darier.27 In 1929 Groenblad and Strandberg recognized the combination of skin and eye abnormalities for the first time.52., 132.
The most common presentation of skin lesions involves ivory to yellowish-colored, raised papules varying in size from 1–3 mm. The papules may have a linear or reticular arrangement and may coalesce into plaques.125 Sometimes larger confluent areas with
The skin
The classic histological picture of PXE skin is elastin abnormality in the mid-epidermis with normal morphology in the papillary and deep dermal layers.87
The elastin band undergoes swelling, granular degeneration, and fragmentation; splitting and curling of elastin fibers gives it the appearance of an iron wool scouring pad upon Von Kossa staining.75., 90., 117. In the abnormal granular elastin matrix, calcium depositions (CaCO3and CaPO4) were found.87 In addition, the presence of proteoglycans
Classification of PXE
From the previous sections describe, it may be clear that the diagnosis of PXE may be quite difficult. Neither the skin lesions nor the AS by themselves are pathognomonic. Von Kossa staining in skin biopsies will probably more often solve a diagnostic problem than demonstration of AS, because the differential diagnosis of elastin changes in a skin biopsy contains fewer disorders than the differential diagnosis of AS (Table 2). The comet-like tails in the retina seem to be pathognomonic for PXE
Mode of inheritance
The majority of PXE patients are sporadic cases. In PXE families with a discernible mode of inheritance, AR inheritance is much more common than AD segregation.102., 103., 104., 144. In PXE families, multiple affected siblings are common, but multigenerational transmission is rare. Initially, some investigators have attempted to subtype PXE based both on phenotypic expression and inheritance. Pope et al suggested, on the basis of the phenotype alone, that there are two AD and two AR forms of
Transport function of ABCC6 in relation to PXE
At present, the relationship between biomolecules transported by ABCC6 and the PXE disease phenotype is not clear. Given the high expression of ABCC6 in kidney and liver, it is possible that PXE is in fact a heritable systemic disorder.142 In this scenario, a primary defect of ABCC6 in liver and kidney could result in abnormal levels of ABCC6 substrates in the blood, which could affect the elastic fiber assembly at specific sites in the body. On the other hand, (lower) ABCC6 expression also has
Future prospects
The recent progress in the identification of the gene for PXE is a significant step. New insights in the etiology of the disease have opened up new research avenues, but many questions remain. The functional consequences of mutations in ABCC6 gene are not yet understood. It is essential to obtain additional genetic mutation and phenotypic data for a complete overview of all mutations that lead to PXE. With these data, further insight will be gained in the genotype–phenotype relationship and the
Method of literature search
Medline, PubMed, and OVID search of relevant literature spanning the period 1966 to January 2002 was performed. Search terms were the following: ATP-binding cassette transporter, (autosomal dominant) angioid streaks, Bruch's membrane, classification, differential diagnosis, elastic fibers, hereditary angioid streaks, pseudoxanthoma elasticum, photoreceptor, retina, and retinal pigment epithelium. Additional references included standard textbooks on biology and biochemistry of the eye as well as
Acknowledgements
The authors acknowledge with gratitude Ms. S. Terry (PXE International Committee) for her support and helpful comments. We would like to thank. L. Kornet, PhD, for stimulating comments. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
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2016, Current Opinion in PharmacologyCitation Excerpt :As previously highlighted, PPi not only acts as a potent inhibitor of connective tissue calcification, but also contributes directly to the calcification process. Intriguingly, one of the identified sources of systemic PPi is through ATP binding cassette sub-family C member 6 (ABCC6)-mediated ATP release from hepatocytes [16]. Still within the vasculature of the liver, released ATP is rapidly converted to PPi and AMP by ENPP1, which are in turn distributed throughout the body via the circulation.