A delayed presentation of homozygous protein C deficiency in a series of children: a report on two molecular defects

Baothman, Abdullah; Alsobhi, Enaam; Khayat, Hassan A.; Alsulami, Raed; Alkahtani, Abdulaziz S.; Al-Thobyani, Abdelraheem A.; Marzouk, Yousef; Abdelaal, Mohammad A.

doi:10.1002/ccr3.699

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…Another study in Saudi Arabia reported that intracranial bleeding was noted at a lower frequency than PF, and intracranial atrophy and fibrosis were also noted, however, blindness early in life was a common outcome [24]. A literature review of 82 patients with homozygous PC deficiency from 1984 to 2014 showed that PF occurred in 53 patients (65%), blindness occurred in 16 patients (20%) and intracranial hemorrhage occurred in 8 patients (10%) [24]. Blindness is a common manifestation of severe PC deficiency and may arise from vitreal bleeding or from retinal vein, artery or vitreal vein thromboses with retinal detachment manifesting as leukocoria or ischemic optic atrophy [25,26].…”

Section: Discussionmentioning

confidence: 97%

“…ICTH preceded PF in both of the affected patients. Another study in Saudi Arabia reported that intracranial bleeding was noted at a lower frequency than PF, and intracranial atrophy and fibrosis were also noted, however, blindness early in life was a common outcome [24]. A literature review of 82 patients with homozygous PC deficiency from 1984 to 2014 showed that PF occurred in 53 patients (65%), blindness occurred in 16 patients (20%) and intracranial hemorrhage occurred in 8 patients (10%) [24].…”

Section: Discussionmentioning

confidence: 99%

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Clinical and genetic features of Chinese pediatric patients with severe congenital protein C deficiency who first presented with purpura fulminans: A case series study and literature review

Tang

Zhang

Yang

et al. 2022

Thrombosis Research

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Introduction: Purpura fulminans (PF) is a hematological emergency that can be caused by severe congenital protein C (PC) deficiency. It has been rarely reported in the Chinese population. We aimed to characterize the clinical and genetic features of Chinese pediatric patients with severe congenital PC deficiency who first presented with PF. Materials and methods: Twelve pediatric patients were diagnosed with severe congenital PC deficiency with PF, which was diagnosed based on our hospital records and previous reports from 1988 to July 2021 in China. We evaluated the clinical and genetic features of these patients. Results: Nine patients (9/12, 75%) had onsets that were observed within the first 48 h after birth. Six patients had a family history of thromboembolism. There was no consanguinity. Other symptoms were intracranial thrombosis or hemorrhage (4, 33.3%), ocular lesions (2, 16.7%), gastrointestinal hemorrhage (2, 16.7%) and kidney infarction before birth (1, 8.3%). All but one of the patients (one case not detected) had a plasma PC activity of <10%. The genetic study indicated that in the eight patients with inherited PC deficiency, two were homozygous, five were compound heterozygous and one was heterozygous for PC deficiency. Conclusion: This is the first and largest case series of Chinese pediatric patients with severe congenital PC deficiency who first presented with PF. It has been shown that treatment with both fresh frozen plasma and anticoagulants is recommended when PC concentrate is not easily available, especially in developing countries.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Clinical and genetic features of Chinese pediatric patients with severe congenital protein C deficiency who first presented with purpura fulminans: A case series study and literature review

Tang

Zhang

Yang

et al. 2022

Thrombosis Research

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“…Furthermore, protein C enhances fibrinolysis by neutralizing circulating plasminogen activator inhibitor and augmenting tissue plasminogen activator activity. 20 A deficiency in protein C can increase the risk of thrombosis, and there are two types of congenital protein C deficiency: Type I, defined by reduced antigenic levels and function, and Type II, characterized by diminished function while maintaining normal antigenic levels. The Human Gene Mutation Database contains more than 390 PROC mutations, including missense, nonsense, insertion, deletion, and splicing mutations, with missense mutations accounting for over 65% of all PROC mutations.…”

Section: Discussionmentioning

confidence: 99%

Digenic Inheritance of PROC and SERPINC1 Mutations Contributes to Multiple Sites Venous Thrombosis

Li,

Zhu,

et al. 2024

Hamostaseologie

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Venous thromboembolism (VTE) represents a worldwide health challenge, impacting millions of people each year. The genesis of venous thrombosis is influenced in part by genetic components. Hereditary thrombosis is described as a genetically determined susceptibility to VTE. In the present study, a male patient was referred to our department presenting with multiple venous thrombosis events in different locations. Given a lack of identifiable risk factors, we aimed to investigate the possible genetic factor underlying venous thrombosis. Whole-exome sequencing was employed to examine genes linked to inherited thrombophilia in the proband. Putative variants were subsequently confirmed through Sanger sequencing within the family. The proband was identified as carrying two genetic mutations. One is the novel c.400G > C (p.E134Q) mutation affecting the final nucleotide of exon 5 in the PROC gene, potentially impacting splicing. The other is a previously reported heterozygous nonsense variant c.1016G > A (p.W339X) in the SERPINC1 gene. The proband inherited the former from her mother and the latter from her father. The presence of digenic inheritance in the patient reflects the complex phenotype of venous thrombosis and demonstrates the significance of an unbiased approach to detect pathogenic variants, especially in patients with a high risk of hereditary thrombosis.

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“…Total retinal detachment and a left macular hemorrhage Paysse EA [2002] [ 19 ] 1 OU Flat anterior chamber Bilateral retinal detachment, fibrotic hyaloid arteries Sirachainan N et al [2003] [ 20 ] 2 OU Preserving eye function, high myopia, cerebral palsy Park UC et al [2005] [ 21 ] 1 OU Bilateral corneal opacity, microphthalmia, posterior synechia, pupillary membrane, shallow anterior chamber Vitreoretinopathy suggesting, PHPV, intravitreal masses, funnel-shaped retinal detachment with bilateral retinal dysplasia Bilateral leukocoria, no microphthalmos, blind OU de Lemus-Varela ML [2005) [ 22 ] 1 OU Vitreous hemorrhage Douglas AG et al [2010] [ 23 ] 1 OU No red reflex OU Vitreoretinal dysplasia, severe hazy media in one eye and OU PFV Leukocoria OS, bilateral microphthalmia,, deranged VEP, poor vision, nystagmus Wang BZ [2012] [ 24 ] 1 OU Macular hypoplasia with blond retinal background Doll’s eye movements, no fix and follow movement of the eyes, ponto-cerebellar hypoplasia, nystagmus, strabismus, Flat ERG Desai S et.al. [2014] [ 25 ] 1 OU Combined central retinal venous and arterial obstruction Severe Type II protein C deficiency with factor V Leiden mutation, Glaucoma Almarzouki HS et al [2016] [ 26 ] 2 OU Peter’s anomaly Baothman AA et al [2017] [ 27 ] 5 OU Peter’s anomaly, corneal opacity (3/5) Blindness (4/5OU), ocular hemorrhage shortly after birth resulted in visual loss (1/5) Present study 1 OU Left eye shallow anterior chamber, cataract...…”

Section: Discussionmentioning

confidence: 99%

Ophthalmic manifestations of congenital protein C deficiency: a case report and mini review

2020

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Background: Homozygous protein C (PC) deficiency is a potentially fatal disease with ocular blinding presentation or sequela. Case presentation: A 5 month-old boy was presented for evaluation of leukocoria. He had a history of frequent bruises and PC deficiency, treated with warfarin. His intraocular pressure was normal. In the left eye leukoma with anterior segment dysgenesis, shallow anterior chamber, and cataract were observed. Fundus was not visible. B-scan revealed a closed funnel retinal detachment. His right eye had a normal anterior segment and a thin retina with anomalous retinal vascular branching at equator and peripheral retina. A fibrovascular tuft on the optic nerve head with induced traction on superior arcade was visible. Total loss of a and b wave of both were appreciated in electroretinography (ERG). Fluorescein angiography (FA) showed very severe leakage at the junction of the vascularized and non-vascularized retina and optic nerve head. Favorable outcome was achieved with lasering of avascular retina in the right eye. Conclusion: The potential for protein C deficiency should be assessed in all infants with leukocoria, anterior segment dysgenesis, retinal detachment and retinal dysplasia. Early diagnosis could save the child's life and vision.

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A delayed presentation of homozygous protein C deficiency in a series of children: a report on two molecular defects

Cited by 11 publications

References 30 publications

Clinical and genetic features of Chinese pediatric patients with severe congenital protein C deficiency who first presented with purpura fulminans: A case series study and literature review

Clinical and genetic features of Chinese pediatric patients with severe congenital protein C deficiency who first presented with purpura fulminans: A case series study and literature review

Digenic Inheritance of PROC and SERPINC1 Mutations Contributes to Multiple Sites Venous Thrombosis

Ophthalmic manifestations of congenital protein C deficiency: a case report and mini review

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