Characterization of a Pseudoxanthoma elasticum-like patient with coagulation deficiency, cutaneous calcinosis and GGCX compound heterozygosity

Pseudoxanthoma elasticum‐like syndrome with coagulation deficiency associated with carotid artery hypoplasia and a novel gamma‐glutamyl carboxylase gene mutation

“…GGCX mutations may cause PXE‐like with coagulation deficiency, congenital deficiency of VK‐dependent coagulation factors (VKCFD), PXE/PXE‐like overlap syndrome, and PXE‐like with pigmentary retinopathy 4 . Five phenotypes have been described depending on ophthalmological, dermal, cardiac, osseous, and coagulation abnormalities, leading to a wide spectrum of disease that includes PXE with ophthalmological and dermatological symptoms, VKCFD, or fetal warfarin syndrome with cardiac, skeletal, and facial abnormalities 1,4 …”

“…Histological features of PXE‐like syndrome include calcifications and fragmentation of elastic fibers 1,2 …”

“…Vanakker et al described the ultrastructural and molecular findings in 2007. 1,2 We present the case of a 40-year-old male born from non- tissues. 3,4 GGCX mutations may cause PXE-like with coagulation deficiency, congenital deficiency of VK-dependent coagulation factors (VKCFD), PXE/PXE-like overlap syndrome, and PXElike with pigmentary retinopathy.…”

“…4 Five phenotypes have been described depending on ophthalmological, dermal, cardiac, osseous, and coagulation abnormalities, leading to a wide spectrum of disease that includes PXE with ophthalmological and dermatological symptoms, VKCFD, or fetal warfarin syndrome with cardiac, skeletal, and facial abnormalities. 1,4 Histological features of PXE-like syndrome include calcifications and fragmentation of elastic fibers. In conclusion, our findings expand the vascular and allelic variants of this rare disease.…”

γ-Glutamyl carboxylase mutations differentially affect the biological function of vitamin K–dependent proteins

“…5,[30][31][32][33] Genetic screenings of patients with vitamin K-related disorders have identified more than 40 naturally occurring mutations in GGCX. 17,34,35 Clinical manifestations of these mutations have been classified into 5 distinct phenotypes: the bleeding phenotype (VKCFD) and the nonbleeding phenotypes of cardiac, dermatologic, ophthalmologic, and osseous symptoms. 17 VKCFD results from insufficient carboxylation of VKD coagulation factors in the liver and can be ameliorated through the administration of high doses of vitamin K. 15 However, nonbleeding phenotypes, caused by defects in carboxylation of extrahepatic Gla proteins, seem to be more difficult to rescue and require much higher doses of vitamin K. 25,36 Importantly, some GGCX-associated nonbleeding phenotypes (eg, osseous symptoms) overlap clinically with other syndromes, such as the fetal warfarin syndrome (an embryo disorder resulting from fetal exposure to maternal ingestion of warfarin during pregnancy).…”