Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency: Difference between revisions

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==Overview==
==Overview==
Pseudoxanthoma elasticum (PXE)-like disorder with multiple coagulation factor deficiency is caused by homozygous or compound heterozygous mutation in the gene encoding gamma-glutamyl carboxylase on chromosome 2p11.<ref>http://omim.org/entry/610842</ref>
Pseudoxanthoma elasticum (PXE)-like disorder with multiple coagulation factor deficiency is caused by homozygous or compound heterozygous mutation in the gene encoding gamma-glutamyl carboxylase on chromosome 2p11.<ref>http://omim.org/entry/610842</ref>
==Histopathology==
Vanakker et al described this as a disorder sharing features of pseudoxanthoma elasticum and cutis laxa and associated with multiple coagulation factor deficiency. A PXE-like disorder with multiple coagulation factor deficiency had been described in case reports by MacMillan and Vickers , Rongioletti et al., and Le Corvaisier-Pieto et al.


==Pathophysiology==
==Pathophysiology==
Vanakker et al described this as a disorder sharing features of pseudoxanthoma elasticum and cutis laxa and associated with multiple coagulation factor deficiency. Clinical overlap of PXE  from the skin manifestations of yellowish papules or leathery plaques, with dot-like depressions at presentation, angioid streaks and/or ocular peau d'orange, and fragmentation and calcification of elastic fibers in the dermis. Important phenotypic differences from PXE included much more severe skin laxity with involvement of the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. By light microscopy, the changes in the reticular dermis were identical to those typical of PXE: elastic fibers were polymorphous, fragmented, and mineralized, as shown by von Kossa stain. On the ultrastructural level, however, elastic fibers had a more fragmented and mottled appearance than that observed typically in PXE. funduscopy revealed only limited angioid streaks and/or peau d'orange and visual acuity was normal in all patients.
Clinical overlap of PXE  from the skin manifestations of yellowish papules or leathery plaques, with dot-like depressions at presentation, angioid streaks and/or ocular peau d'orange, and fragmentation and calcification of elastic fibers in the dermis. Important phenotypic differences from PXE included much more severe skin laxity with involvement of the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. By light microscopy, the changes in the reticular dermis were identical to those typical of PXE: elastic fibers were polymorphous, fragmented, and mineralized, as shown by von Kossa stain. On the ultrastructural level, however, elastic fibers had a more fragmented and mottled appearance than that observed typically in PXE. funduscopy revealed only limited angioid streaks and/or peau d'orange and visual acuity was normal in all patients.
 
A PXE-like disorder with multiple coagulation factor deficiency had been described in case reports by MacMillan and Vickers , Rongioletti et al., and Le Corvaisier-Pieto et al.  


==Diagnosis==
===Symptoms===
===Laboratory findings===
Cardiovascular investigations showed subclinical atherosclerotic plaques in the lower limbs  and vascular occlusion with intermittent claudication, cerebral aneurysms. Clinical manifestations of the coagulation defects were  meningeal hemorrhages, a postpartum hemorrhage after delivery of a child, and  unexplained hematemesis. Another patient had a history of epistaxis, spontaneous gingival bleeding, and severe vaginal hemorrhages.
Cardiovascular investigations showed subclinical atherosclerotic plaques in the lower limbs  and vascular occlusion with intermittent claudication, cerebral aneurysms. Clinical manifestations of the coagulation defects were  meningeal hemorrhages, a postpartum hemorrhage after delivery of a child, and  unexplained hematemesis. Another patient had a history of epistaxis, spontaneous gingival bleeding, and severe vaginal hemorrhages.



Revision as of 20:57, 21 December 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Jyostna Chouturi, M.B.B.S [2]

Synonyms and keywords: Pseudoxanthoma elasticum- like disorder with multiple coagulation factor deficiency

Overview

Pseudoxanthoma elasticum (PXE)-like disorder with multiple coagulation factor deficiency is caused by homozygous or compound heterozygous mutation in the gene encoding gamma-glutamyl carboxylase on chromosome 2p11.[1]

Histopathology

Vanakker et al described this as a disorder sharing features of pseudoxanthoma elasticum and cutis laxa and associated with multiple coagulation factor deficiency. A PXE-like disorder with multiple coagulation factor deficiency had been described in case reports by MacMillan and Vickers , Rongioletti et al., and Le Corvaisier-Pieto et al.

Pathophysiology

Clinical overlap of PXE from the skin manifestations of yellowish papules or leathery plaques, with dot-like depressions at presentation, angioid streaks and/or ocular peau d'orange, and fragmentation and calcification of elastic fibers in the dermis. Important phenotypic differences from PXE included much more severe skin laxity with involvement of the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. By light microscopy, the changes in the reticular dermis were identical to those typical of PXE: elastic fibers were polymorphous, fragmented, and mineralized, as shown by von Kossa stain. On the ultrastructural level, however, elastic fibers had a more fragmented and mottled appearance than that observed typically in PXE. funduscopy revealed only limited angioid streaks and/or peau d'orange and visual acuity was normal in all patients.

Diagnosis

Symptoms

Laboratory findings

Cardiovascular investigations showed subclinical atherosclerotic plaques in the lower limbs and vascular occlusion with intermittent claudication, cerebral aneurysms. Clinical manifestations of the coagulation defects were meningeal hemorrhages, a postpartum hemorrhage after delivery of a child, and unexplained hematemesis. Another patient had a history of epistaxis, spontaneous gingival bleeding, and severe vaginal hemorrhages.

Molecular Genetics

PXE-like phenotype with multiple vitamin K-dependent clotting factors mutations in the GGCX gene  which encodes an enzyme important for gamma-carboxylation of Gla proteins. The authors found homozygosity for a missense mutation and compound heterozygosity PXE-like disorder with multiple coagulation factor deficiency is inherited as a recessive.

In 2 sisters with PXE-like disorder and multiple coagulation factor deficiency, Li et al. (2009) identified compound heterozygosity for the V255M (137167.0012) and S300F (137167.0013) mutations in the GGCX gene. Skin biopsies from the patients showed undercarboxylated matrix gla proteins (MGP; 154870) in the areas of abnormal mineralization.

References