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Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80%) and ligneous gingivitis (34%), followed by less common manifestations such as ligneous vaginitis (8%), and involvement of the respiratory tract (16%), the ears (14%), or the gastrointestinal tract (2%). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34% of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T, P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLG proteins as a common molecular pathomechanism in type I PLG deficiency. IntroductionPlasminogen (PLG) plays an important role in intra-and extravascular fibrinolysis, wound healing, cell migration, angiogenesis, and embryogenesis. 1 Plg is primarily synthesized by liver tissue. 2 However, other minor sources identified in mice include adrenal gland, kidney, brain, testis, heart, lung, uterus, spleen, thymus, and gut tissue. 3 In humans, the cornea has been described as an extrahepatic site of PLG synthesis. 4 Inherited PLG deficiency in humans can be divided into 2 types: true PLG deficiency (type I, or hypoplasminogenemia) and dysplasminogenemia (type II). In the former, both immunoreactive PLG level and functional activity are reduced, while the latter shows a normal or slightly reduced level of immunoreactive PLG while functional activity is significantly decreased. It has been shown by several authors since 1995 that homozygous or compound-heterozygous type I PLG deficiency is a major cause of a rare inflammatory disease affecting mainly mucous membranes in different body sites. 5,6 The most common clinical manifestation is ligneous conjunctivitis, characterized by development of fibrin-rich, woodlike ("ligneous") pseudomembranous lesions. Involvement of the cornea may result in blindness. Other, less common manifestations are ligneous gingivitis, otitis media, ligneous bronchitis and pneumonia, involvement of the gastrointestinal or female genital tract, juvenile colloid milium of the skin, and congenital occlusive hydrocephalus. 6 In severely affected patients, prognosis is poor and treatment options are few. Worldwide, more than 150 patients with this disease have been reported since 1847, the date of first description. 6,7 From the Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany; For personal use o...

Generalized membranous gingival enlargement due to accumulation of amyloid or fibrin-like material is a rare, destructive and poorly defined disease entity. Some patients also show extraoral manifestations. The lesion is an involvement of periodontal tissues caused by the same process as ligneous conjunctivitis. In this report, 3 new cases, two of whom are siblings, are presented. Defective fibrinolysis and abnormal wound healing seem to be the main pathogenetic mechanism of this unusual disease, which should be evaluated systemically considering other mucosal involvement.

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Hyaline or amyloid-like substances may be seen in several oral lesions. Some of these originate from epithelial cells and some from connective tissue components. In this study, amyloid-like material causing gingival enlargement in three patients, with eyelid involvement in two, was examined using histochemistry, immunohistochemistry and electron microscopy. These accumulations did not share the classical features of amyloid such as green birefringence under polarized light after Congo red staining. Our findings suggest that epithelial degeneration plays an important role in the pathogenesis of these amyloid-like accumulations. These substances may be the result of defective amyloidogenesis and our cases may represent an oral counterpart of ligneous conjunctivitis or colloid milium of the skin.