Pseudoxanthoma Elasticum and Sudden Death

Abstract

Pseudoxanthoma elasticum (PXE) is a generalized connective tissue disorder in which there is calcification of elastic fibers within arteries, eyes, and skin. Characteristic features include yellow-orange papular skin lesions, angioid streaks radiating out from the optic discs, and arterial calcification. The prevalence in the general population varies widely from 1/70,000 to 1/160,000. PXE has an autosomal recessive inheritance pattern and results from mutations in the ATP-binding cassette transporter C6 (ABCC6) that has been mapped to 16p13.1. Over 300 loss-of-function mutations have been identified. Individuals with PXE may come to forensic attention because of sudden death involving accelerated coronary atherosclerosis with acute myocardial ischemia, systemic hypertension, mitral valve prolapse, restrictive cardiomyopathy, gastrointestinal hemorrhage, and cerebral ischemia or hemorrhage. Because of the heritable nature of the disease, family counseling and screening are in order when previously unsuspected cases are encountered at autopsy.

The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

“…Clinical manifestations are usually detected from the second or third decade onwards, while being rarely present at birth [25,26]. The first to occur are usually the cutaneous manifestations of PXE, consisting of small xanthoma-like yellowish papules or larger plaques formed by coalesced papules [27,28]. These lesions typically appear first on the lateral side of the neck while other regions, mainly flexural zones, such as the axillae, antecubital, and popliteal fossae, groins, and peri-umbilical skin, become affected during further disease progression [28].…”

“…If a skin biopsy is taken, histopathological examination using conventional hematoxylin-eosin (HE) staining reveals distinct microscopic features, such as fragmentation and clumping of short and thick elastic fibers, typically located in the mid-dermis. Alternative staining procedures, like Von Kossa, Verhoeff–Van Gieson, and Alizarin Red, show pronounced calcium deposits and an increased amount of elastin in the dermis [27]. Furthermore, abnormal collagen fibrils can be observed near the calcified elastic fibers as well as abnormal amounts of proteoglycans and glycosaminoglycans [29].…”

“…The earliest ocular manifestation of PXE which can be seen with funduscopy is peau d’orange, a lesion consisting of small dark spots mainly localized temporal to the macula [24,26]. Later in life, elastic fibers in Bruch’s membrane of the eye become progressively calcified and fragmented, causing cracks in the membrane that manifest as angioid streaks, dark lines extending outward from the optic disk [27]. Due to this fragmentation of Bruch’s membrane, choroidal neovascularization (CNV), in which newly formed, but fragile blood vessels penetrate the membrane, is able to take place.…”

Pseudoxanthoma Elasticum: A Pediatric Case

“…Ortalama başlangıç yaşı 13,5'tir, herhangi bir yaşta da ortaya çıkabilir. Kadınlarda erkeklere göre iki kat daha sık ortaya çıkar (1,7).…”

“Eyeing” the Cause of Heart Failure: Visible Telltale Clues

“…Cardiovascular complications result primarily from advanced atherosclerosis, which in turn leads to greatly diminished peripheral pulses, coronary artery occlusion and calcification, left ventricular dysfunction, and sometimes sudden death. 2 The patient in the photograph looked much older than her 42 years. She had experienced long-standing angina pectoris, almost absent peripheral pulses, angioid streaks in both optic fundi, and radiographically detectable calcifications of her coronary arteries.…”