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Severe hypoplasminogenemia (HPG) or type 1 plasminogen (plg) deficiency is a systemic disease characterised by markedly impaired extracellular fibrinolysis leading to the formation of ligneous (fibrin-rich) pseudomembranes on mucosae during wound healing.
ORPHA:722Classification level: Disorder
Prevalence of severe HPG is in the range of 1.6/1,000,000.
Onset of clinical manifestations usually occurs in early infancy, but can occur at any age, and may be triggered by repetitive microtrauma (dust, a foreign body), surgical procedures or local inflammation. The most common clinical manifestation of HPG is inflammation of the conjunctivae (ligneous conjunctivitis (LC); see this term). Other sites of involvement include the upper (ligneous periodontitis) and lower gastrointestinal tract (duodenal ulcers), the respiratory tract (pseudomembranous laryngitis, bronchitis and pneumonia) and the female genital tract (vaginitis, cervicitis, involvement of the fallopian tube, ovary and endometrium). The central nervous system (occlusive hydrocephalus, Dandy Walker malformation) and the skin (juvenile colloid milium) may also be affected. Severe HPG is not a risk factor for thrombophilia.
Severe HPG is caused by homozygous or compound-heterozygous mutations in the plasminogen gene (PLG; 6q26). In severe HPG, PLG mutations result in parallel reductions in both the level of immunoreactive plg and its functional activity, thus specific plg activity is normal. Subjects with heterozygous HPG (with plg antigen concentrations and plg residual activities at around 50%) are asymptomatic with regard to extracellular fibrinolysis. In dysplasminogenemia (DPG, type II plg deficiency), plg levels are normal or slightly reduced, but specific functional plg activity is markedly reduced. Individuals with isolated DPG are asymptomatic.
Diagnosis of severe HPG relies on recognition of the clinical manifestations and on the results of laboratory tests for active and immunoreactive plg levels. Diagnosis can be confirmed by analysis of the PLG gene.
Prenatal diagnosis is possible in families in which the PLG mutation has been identified.
Although most cases are sporadic, autosomal recessive inheritance has been reported.
Management and treatment
Management depends on the sites involved. At present, treatment strategies are mainly targeted towards management of LC (see this term). There is no established therapy available for patients with systemic multiorgan involvement. Treatment with hormones (levonorgestrel and ethinyl estradiol) or high dose corticosteroids has been shown to be successful in single cases. Occlusive hydrocephalus requires implantation of a ventriculoperitoneal or ventriculoatrial shunt.
In milder cases were only the conjunctivae are involved the visual prognosis is moderate, however, the prognosis for severe cases with multiorgan involvement is very poor.