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Plasminogen deficiency, type I

MedGen UID:
369859
Concept ID:
C1968804
Disease or Syndrome
Synonyms: Hypoplasminogenemia; Type 1 plasminogen deficiency
SNOMED CT: Dysplasminogenemia (95844003)
 
Gene (location): PLG (6q26)
 
Monarch Initiative: MONDO:0009009
OMIM®: 217090

Definition

Congenital plasminogen deficiency is a rare autosomal recessive disorder characterized clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. A slightly increased female:male ratio has been observed (1.4:1 to 2:1) (Schuster and Seregard, 2003; Tefs et al., 2006). Type I plasminogen deficiency is characterized by decreased serum plasminogen activity, decreased plasminogen antigen levels, and clinical symptoms, whereas type II plasminogen deficiency, also known as 'dysplasminogenemia,' is characterized by decreased plasminogen activity with normal or slightly reduced antigen levels. Patients with type II deficiency are usually asymptomatic. Ligneous conjunctivitis and pseudomembranous formation has only been associated with type I plasminogen deficiency. Presumably, normal amounts of plasminogen antigen with decreased activity, as seen in type II, is sufficient for normal wound healing (Schuster and Seregard, 2003). [from OMIM]

Additional description

From MedlinePlus Genetics
Congenital plasminogen deficiency is a disorder that results in inflamed growths on the mucous membranes, which are the moist tissues that line body openings such as the eyelids and the inside of the mouth. Development of the growths are usually triggered by infections or injury, but they may also occur spontaneously in the absence of known triggers. The growths may recur after being removed.

Congenital plasminogen deficiency most often affects the conjunctiva, which are the mucous membranes that protect the white part of the eye (the sclera) and line the eyelids. A characteristic feature of this disorder is ligneous conjunctivitis, in which a buildup of a protein called fibrin causes inflammation of the conjunctiva (conjunctivitis) and leads to thick, woody (ligneous), inflamed growths that are yellow, white, or red. Ligneous conjunctivitis most often occurs on the inside of the eyelids. However, in about one-third of cases, ligneous conjunctivitis over the sclera grows onto the cornea, which is the clear covering that protects the colored part of the eye (the iris) and pupil. Such growths can tear the cornea or cause scarring. These corneal problems as well as obstruction by growths inside the eyelid can lead to vision loss.

People with congenital plasminogen deficiency may also develop ligneous growths on other mucous membranes, including the inside of the mouth and the gums; the lining of the nasal cavity; and in females, the vagina. Growths on the mucous membranes that line the gastrointestinal tract may result in ulcers. The growths may also develop in the windpipe, which can cause life-threatening airway obstruction, especially in children. In a small number of cases, affected individuals are born with impaired drainage of the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF), resulting in a buildup of this fluid in the skull (occlusive hydrocephalus). It is unclear how this feature is related to the other signs and symptoms of congenital plasminogen deficiency.  https://medlineplus.gov/genetics/condition/congenital-plasminogen-deficiency

Clinical features

From HPO
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Duodenal ulcer
MedGen UID:
41670
Concept ID:
C0013295
Disease or Syndrome
An erosion of the mucous membrane in a portion of the duodenum.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Abnormal thrombosis
MedGen UID:
871247
Concept ID:
C4025731
Anatomical Abnormality
Venous or arterial thrombosis (formation of blood clots) of spontaneous nature and which cannot be fully explained by acquired risk (e.g. atherosclerosis).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Dandy-Walker malformation
MedGen UID:
419183
Concept ID:
C2931867
Congenital Abnormality
A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
Nephritis
MedGen UID:
14328
Concept ID:
C0027697
Disease or Syndrome
The presence of inflammation affecting the kidney.
Periodontitis
MedGen UID:
45815
Concept ID:
C0031099
Disease or Syndrome
Inflammation of the periodontium.
Decreased level of plasminogen
MedGen UID:
900318
Concept ID:
C4280715
Finding
A decreased level of Plasminogen
Gingivitis
MedGen UID:
4895
Concept ID:
C0017574
Disease or Syndrome
Inflammation of the gingiva.
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Abnormality of the skin
MedGen UID:
1845238
Concept ID:
C5848159
Anatomical Abnormality
An abnormality of the skin.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation.

Professional guidelines

PubMed

Tefs K, Hügle B, Schuster V
Am J Ophthalmol 2004 Oct;138(4):699; author reply 699-700. doi: 10.1016/j.ajo.2004.05.054. PMID: 15488842

Recent clinical studies

Etiology

Keragala CB, Medcalf RL
Blood 2021 May 27;137(21):2881-2889. doi: 10.1182/blood.2020008951. PMID: 33735914
Ozbek-Uzman S, Yalniz-Akkaya Z, Nurozler Tabakci B, Singar E, Burcu A
Cornea 2021 Mar 1;40(3):299-302. doi: 10.1097/ICO.0000000000002573. PMID: 33290319
Bourrienne MC, Loyau S, Faille D, de Raucourt E, de Mazancourt P, Ho-Tin-Noé B, Gabison E, Ajzenberg N
Thromb Haemost 2020 May;120(5):758-767. Epub 2020 May 5 doi: 10.1055/s-0040-1709526. PMID: 32369847
Song Y, Izumi N, Potts LB, Yoshida A
BMJ Case Rep 2014 May 19;2014 doi: 10.1136/bcr-2014-204138. PMID: 24842363Free PMC Article
Yoo H, Kim HJ, Yi CA, Cho YY, Joung JY, Jeong H, Jeon K
J Korean Med Sci 2013 Jun;28(6):959-61. Epub 2013 Jun 3 doi: 10.3346/jkms.2013.28.6.959. PMID: 23772166Free PMC Article

Diagnosis

Quintero-Estades JA, Iacob CE, Donnenfeld ED, Perry HD
Cornea 2023 Jan 1;42(1):118-120. Epub 2022 Sep 29 doi: 10.1097/ICO.0000000000003154. PMID: 36459582
Caputo R, Shapiro AD, Sartori MT, Leonardi A, Jeng BH, Nakar C, Di Pasquale I, Price FW Jr, Thukral N, Suffredini AL, Pino L, Crea R, Mathew P, Calcinai M
Ophthalmology 2022 Aug;129(8):955-957. Epub 2022 Mar 26 doi: 10.1016/j.ophtha.2022.03.019. PMID: 35346720
Keragala CB, Medcalf RL
Blood 2021 May 27;137(21):2881-2889. doi: 10.1182/blood.2020008951. PMID: 33735914
Rouatbi A, Chebbi A, Bouguila H
J Fr Ophtalmol 2018 Dec;41(10):916-919. Epub 2018 Nov 12 doi: 10.1016/j.jfo.2018.03.012. PMID: 30442487
Chiang WY, Liu TT, Huang WT, Kuo MT
Indian J Ophthalmol 2016 Jul;64(7):532-4. doi: 10.4103/0301-4738.190154. PMID: 27609168Free PMC Article

Therapy

Ghassemi H, Atighehchian M, Amoli FA
Digit J Ophthalmol 2022;28(4):110-115. Epub 2022 Oct 28 doi: 10.5693/djo.02.2022.08.005. PMID: 36660187Free PMC Article
Keragala CB, Medcalf RL
Blood 2021 May 27;137(21):2881-2889. doi: 10.1182/blood.2020008951. PMID: 33735914
Martins TGDS, Martins TGDS, Martins DGDS, Kuba MCF
Einstein (Sao Paulo) 2019 Jun 13;17(3):eRC4714. doi: 10.31744/einstein_journal/2019RC4714. PMID: 31215592Free PMC Article
Celkan T
J Thromb Thrombolysis 2017 Jan;43(1):132-138. doi: 10.1007/s11239-016-1416-6. PMID: 27629020
Yoo H, Kim HJ, Yi CA, Cho YY, Joung JY, Jeong H, Jeon K
J Korean Med Sci 2013 Jun;28(6):959-61. Epub 2013 Jun 3 doi: 10.3346/jkms.2013.28.6.959. PMID: 23772166Free PMC Article

Prognosis

Xu L, Sun Y, Yang K, Zhao D, Wang Y, Ren S
Ophthalmic Genet 2021 Apr;42(2):105-109. Epub 2021 Jan 11 doi: 10.1080/13816810.2020.1867753. PMID: 33427557
Bourrienne MC, Loyau S, Faille D, de Raucourt E, de Mazancourt P, Ho-Tin-Noé B, Gabison E, Ajzenberg N
Thromb Haemost 2020 May;120(5):758-767. Epub 2020 May 5 doi: 10.1055/s-0040-1709526. PMID: 32369847
Chiang WY, Liu TT, Huang WT, Kuo MT
Indian J Ophthalmol 2016 Jul;64(7):532-4. doi: 10.4103/0301-4738.190154. PMID: 27609168Free PMC Article
Tananuvat N, Charoenkwan P, Ohazama A, Ketuda Cairns JR, Kaewgahya M, Kantaputra PN
Eur J Med Genet 2014 Nov-Dec;57(11-12):630-5. Epub 2014 Sep 30 doi: 10.1016/j.ejmg.2014.09.006. PMID: 25281489
Song Y, Izumi N, Potts LB, Yoshida A
BMJ Case Rep 2014 May 19;2014 doi: 10.1136/bcr-2014-204138. PMID: 24842363Free PMC Article

Clinical prediction guides

Koseoglu ND, Ceylaner S, Yildirim N
Cornea 2021 Jun 1;40(6):764-768. doi: 10.1097/ICO.0000000000002702. PMID: 33734159
Ozbek-Uzman S, Yalniz-Akkaya Z, Nurozler Tabakci B, Singar E, Burcu A
Cornea 2021 Mar 1;40(3):299-302. doi: 10.1097/ICO.0000000000002573. PMID: 33290319
Kurtulus Waschulewski I, Gökbuget AY, Christiansen NM, Ziegler M, Schuster V, Wahl G, Götz W
Arch Oral Biol 2016 Dec;72:75-86. Epub 2016 Aug 2 doi: 10.1016/j.archoralbio.2016.07.013. PMID: 27552374
Tunay ZÖ, Özdemir Ö, Acar D, Gül E, Akbay S
Arq Bras Oftalmol 2015 Sep-Oct;78(5):318-9. doi: 10.5935/0004-2749.20150083. PMID: 26466233
Tananuvat N, Charoenkwan P, Ohazama A, Ketuda Cairns JR, Kaewgahya M, Kantaputra PN
Eur J Med Genet 2014 Nov-Dec;57(11-12):630-5. Epub 2014 Sep 30 doi: 10.1016/j.ejmg.2014.09.006. PMID: 25281489

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