scholarly journals Phenotypic Progression of Stargardt Disease in a Large Consanguineous Tunisian Family Harboring New ABCA4 Mutations

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yousra Falfoul ◽  
Imen Habibi ◽  
Ahmed Turki ◽  
Ahmed Chebil ◽  
Asma Hassairi ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Stargardt Disease ◽  
Full Field ◽  
Stage Disease ◽  
Bull’S Eye Maculopathy ◽  
Diffuse Atrophy ◽  
Rpe Atrophy ◽  
End Stage ◽  
Bull's Eye ◽  
Tunisian Family

To assess the progression of Stargardt (STGD) disease over nine years in two branches of a large consanguineous Tunisian family. Initially, different phenotypes were observed with clinical intra- and interfamilial variations. At presentation, four different retinal phenotypes were observed. In phenotype 1, bull’s eye maculopathy and slight alteration of photopic responses in full-field electroretinography were observed in the youngest child. In phenotype 2, macular atrophy and yellow white were observed in two brothers. In phenotype 3, diffuse macular, peripapillary, and peripheral RPE atrophy and hyperfluorescent dots were observed in two sisters. In phenotype 4, Stargardt disease-fundus flavimaculatus phenotype was observed in two cousins with later age of onset. After a progression of 9 years, all seven patients displayed the same phenotype 3 with advanced stage STGD and diffuse atrophy. WES and MLPA identified two ABCA4 mutations M1: c.[(?_4635)_(5714+?)dup; (?_6148)_(6479_+?) del] and M2: c.[2041C>T], p.[R681∗]. In one branch, the three affected patients had M1/M1 causal mutations and in the other branch the two affected patients had M1/M2 causal mutations. After 9-year follow-up, all patients showed the same phenotypic evolution, confirming the progressive nature of the disease. Genetic variations in the two branches made no difference to similar end-stage disease.

scholarly journals Prediction of Function in ABCA4-Related Retinopathy Using Ensemble Machine Learning

2020 ◽  
Vol 9 (8) ◽  
pp. 2428 ◽  
Author(s):  
Philipp L. Müller ◽  
Tim Treis ◽  
Alexandru Odainic ◽  
Maximilian Pfau ◽  
Philipp Herrmann ◽  
...  
Keyword(s):  
Machine Learning ◽  
Visual Impairment ◽  
Age Of Onset ◽  
Outer Nuclear Layer ◽  
Stargardt Disease ◽  
Full Field ◽  
Corrected Visual Acuity ◽  
Ensemble Machine Learning ◽  
Prediction Of Function ◽  
Patient Burden

Full-field electroretinogram (ERG) and best corrected visual acuity (BCVA) measures have been shown to have prognostic value for recessive Stargardt disease (also called “ABCA4-related retinopathy”). These functional tests may serve as a performance-outcome-measure (PerfO) in emerging interventional clinical trials, but utility is limited by variability and patient burden. To address these limitations, an ensemble machine-learning-based approach was evaluated to differentiate patients from controls, and predict disease categories depending on ERG (‘inferred ERG’) and visual impairment (‘inferred visual impairment’) as well as BCVA values (‘inferred BCVA’) based on microstructural imaging (utilizing spectral-domain optical coherence tomography) and patient data. The accuracy for ‘inferred ERG’ and ‘inferred visual impairment’ was up to 99.53 ± 1.02%. Prediction of BCVA values (‘inferred BCVA’) achieved a precision of ±0.3LogMAR in up to 85.31% of eyes. Analysis of the permutation importance revealed that foveal status was the most important feature for BCVA prediction, while the thickness of outer nuclear layer and photoreceptor inner and outer segments as well as age of onset highly ranked for all predictions. ‘Inferred ERG’, ‘inferred visual impairment’, and ‘inferred BCVA’, herein, represent accurate estimates of differential functional effects of retinal microstructure, and offer quasi-functional parameters with the potential for a refined patient assessment, and investigation of potential future treatment effects or disease progression.

scholarly journals Case series of Stargardt's disease: Our experience

2016 ◽  
Vol 7 (2) ◽  
pp. 147
Author(s):  
Syed Abdul Wadud ◽  
Muntasir Bin Shahid ◽  
Sumon Afroz
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Autosomal Recessive ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Case Series ◽  
Macular Dystrophy ◽  
Stargardt Disease ◽  
Bull’S Eye Maculopathy ◽  
Bull's Eye

<p>Stargardt disease is the most common form of juvenile macular degeneration. Clinically, it is characterized by pisciform flecks at lhe level of the retinal pigment epithelium and a bull's-eye maculopathy. Inheritance is usually autosomal recessive, although dominantly inherited case have been described. Both sexes are affected equally. We reported here three cases of Stargardt's macular dystrophy, who are siblings and daughters of non consanguineous parents. In case-1,2 and 3 we found the typical presentation with almost same findings.</p>

scholarly journals Temporal macular thinning: a salient sign of Alport syndrome

2021 ◽  
Vol 3 (3) ◽  
pp. 169-174
Author(s):  
Sharan Silvarajoo ◽  
Wai Yong Zheng ◽  
Jamalia Rahmat
Keyword(s):  
Alport Syndrome ◽  
Anterior Segment ◽  
Posterior Segment ◽  
End Stage Renal Failure ◽  
Corrected Visual Acuity ◽  
Bull’S Eye Maculopathy ◽  
End Stage ◽  
Bull's Eye ◽  
Myopic Astigmatism ◽  
Best Corrected Visual Acuity

Alport syndrome is a hereditary, multisystemic disorder that causes abnormalities of the ear, kidney, and eye. A teenager who was suffering from end-stage renal failure and hearing problems was referred to us suspected of Alport syndrome. He did not have any ocular complaints and wore glasses for myopic astigmatism. His best-corrected visual acuity was 6/7.5 bilaterally. Anterior segment examination was unremarkable. Posterior segment examination showed perimacular dot-andfleck retinopathy with bull’s eye maculopathy. Optical coherence tomography revealed temporal macular thinning. The findings were in keeping with the diagnosis of X-linked Alport syndrome. Ocular findings can help diagnose Alport syndrome. Early detection and treatment can help delay the progression of kidney failure.

scholarly journals G1961E mutant allele in the Stargardt disease gene ABCA4 causes bull's eye maculopathy

2009 ◽  
Vol 89 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Wener Cella ◽  
Vivienne C. Greenstein ◽  
Jana Zernant-Rajang ◽  
Theodore R. Smith ◽  
Gaetano Barile ◽  
...  
Keyword(s):  
Mutant Allele ◽  
Disease Gene ◽  
Stargardt Disease ◽  
Bull’S Eye Maculopathy ◽  
Bull's Eye

scholarly journals Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort

2018 ◽  
Vol 19 (8) ◽  
pp. 2196 ◽  
Author(s):  
Marco Nassisi ◽  
Saddek Mohand-Saïd ◽  
Claire-Marie Dhaenens ◽  
Fiona Boyard ◽  
Vanessa Démontant ◽  
...  
Keyword(s):  
Near Infrared ◽  
Age Of Onset ◽  
Fundus Autofluorescence ◽  
Mutation Spectrum ◽  
Fundus Photography ◽  
Heterozygous Mutation ◽  
Autofluorescence Imaging ◽  
Stargardt Disease ◽  
Full Field ◽  
Uncertain Significance

Here we report novel mutations in ABCA4 with the underlying phenotype in a large French cohort with autosomal recessive Stargardt disease. The DNA samples of 397 index subjects were analyzed in exons and flanking intronic regions of ABCA4 (NM_000350.2) by microarray analysis and direct Sanger sequencing. At the end of the screening, at least two likely pathogenic mutations were found in 302 patients (76.1%) while 95 remained unsolved: 40 (10.1%) with no variants identified, 52 (13.1%) with one heterozygous mutation, and 3 (0.7%) with at least one variant of uncertain significance (VUS). Sixty-three novel variants were identified in the cohort. Three of them were variants of uncertain significance. The other 60 mutations were classified as likely pathogenic or pathogenic, and were identified in 61 patients (15.4%). The majority of those were missense (55%) followed by frameshift and nonsense (30%), intronic (11.7%) variants, and in-frame deletions (3.3%). Only patients with variants never reported in literature were further analyzed herein. Recruited subjects underwent complete ophthalmic examination including best corrected visual acuity, kinetic and static perimetry, color vision test, full-field and multifocal electroretinography, color fundus photography, short-wavelength and near-infrared fundus autofluorescence imaging, and spectral domain optical coherence tomography. Clinical evaluation of each subject confirms the tendency that truncating mutations lead to a more severe phenotype with electroretinogram (ERG) impairment (p = 0.002) and an earlier age of onset (p = 0.037). Our study further expands the mutation spectrum in the exonic and flanking regions of ABCA4 underlying Stargardt disease.

scholarly journals Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis: a cross-sectional multicentre international study with experimental animal model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Péter J. Hegyi ◽  
Alexandra Soós ◽  
Emese Tóth ◽  
Attila Ébert ◽  
Viktória Venglovecz ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Morphological Changes ◽  
International Study ◽  
Study Data ◽  
Cross Sectional ◽  
Clinical Biomarkers ◽  
Stage Disease ◽  
Significant Difference ◽  
End Stage

AbstractChronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.

Massive Perivillous Fibrin Deposition and Chronic Histiocytic Intervillositis a Complication of SARS-CoV-2 Infection

2021 ◽  
pp. 109352662110207
Author(s):  
T Marton ◽  
B Hargitai ◽  
K Hunter ◽  
M Pugh ◽  
P Murray
Keyword(s):  
Placental Insufficiency ◽  
Intrauterine Death ◽  
Fibrin Deposition ◽  
Fetal Demise ◽  
Trophoblastic Cells ◽  
Stage Disease ◽  
Villous Trophoblast ◽  
Fetal Movements ◽  
Active Viral Replication ◽  
End Stage

An emerging complication of COVID-19 (SARS-CoV-2) infection is reported. A 23-year-old patient presented with high temperature and reduced fetal movements at 25 + 5/40 weeks of gestation. RT-PCR proved maternal COVID-19 infection. Ultrasound examination confirmed intrauterine death. Placenta histology showed necrosis of the villous trophoblast, associated with Chronic Histiocytic Intervillositis (CHI) and Massive Perivillous Fibrin Deposition (MPFD) with up to 90% - of the intervillous spaces being involved. Immunohistochemistry showed CD68 positive histiocytes in the intervillous spaces and the villous trophoblast was positive for the COVID-19 spike protein. RNA scope signal was indicative of the presence of the viral genome and active viral replication in the villous trophoblastic cells, respectively. MPFD is a gradually developing end-stage disease with various etiology, including autoimmune and alloimmune maternal response to antigens expressed at the feto-maternal interface and frequently accompanies chronic alloimmune villitis or histiocytic intervillositis. Covid-19 infection is associated with similar pattern of histological changes of the placenta leading to placental insufficiency and fetal death. This case report supports maternal- fetal vertical transmission of SARS-CoV-2 virus leading to placental insufficiency and fetal demise. MPFD and CHI appear to be the typical placental histology for SARS-CoV-2 virus infection associated fetal demise.

scholarly journals Laparoscopy in Liver Transplantation: The Future Has Arrived

HPB Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Quirino Lai ◽  
Rafael S. Pinheiro ◽  
Giovanni B. Levi Sandri ◽  
Gabriele Spoletini ◽  
Fabio Melandro ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Scientific Progress ◽  
Laparoscopic Approach ◽  
Standard Of Care ◽  
Radical Change ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Therapeutic Laparoscopy ◽  
Stage Disease ◽  
End Stage

In the last two decades, laparoscopy has revolutionized the field of surgery. Many procedures previously performed with an open access are now routinely carried out with the laparoscopic approach. Several advantages are associated with laparoscopic surgery compared to open procedures: reduced pain due to smaller incisions and hemorrhaging, shorter hospital length of stay, and a lower incidence of wound infections. Liver transplantation (LT) brought a radical change in life expectancy of patients with hepatic end-stage disease. Today, LT represents the standard of care for more than fifty hepatic pathologies, with excellent results in terms of survival. Surely, with laparoscopy and LT being one of the most continuously evolving challenges in medicine, their recent combination has represented an astonishing scientific progress. The intent of the present paper is to underline the current role of diagnostic and therapeutic laparoscopy in patients waiting for LT, in the living donor LT and in LT recipients.

scholarly journals Diet, nutrients and metabolism: cogs in the wheel driving Alzheimer's disease pathology?

2015 ◽  
Vol 113 (10) ◽  
pp. 1499-1517 ◽  
Author(s):  
Rhona Creegan ◽  
Wendy Hunt ◽  
Alexandra McManus ◽  
Stephanie R. Rainey-Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Aged Care ◽  
Ageing Population ◽  
People With Dementia ◽  
Stage Disease ◽  
Custodial Care ◽  
Global Statistics ◽  
End Stage

Alzheimer's disease (AD), the most common form of dementia, is a chronic, progressive neurodegenerative disease that manifests clinically as a slow global decline in cognitive function, including deterioration of memory, reasoning, abstraction, language and emotional stability, culminating in a patient with end-stage disease, totally dependent on custodial care. With a global ageing population, it is predicted that there will be a marked increase in the number of people diagnosed with AD in the coming decades, making this a significant challenge to socio-economic policy and aged care. Global estimates put a direct cost for treating and caring for people with dementia at $US604 billion, an estimate that is expected to increase markedly. According to recent global statistics, there are 35·6 million dementia sufferers, the number of which is predicted to double every 20 years, unless strategies are implemented to reduce this burden. Currently, there is no cure for AD; while current therapies may temporarily ameliorate symptoms, death usually occurs approximately 8 years after diagnosis. A greater understanding of AD pathophysiology is paramount, and attention is now being directed to the discovery of biomarkers that may not only facilitate pre-symptomatic diagnosis, but also provide an insight into aberrant biochemical pathways that may reveal potential therapeutic targets, including nutritional ones. AD pathogenesis develops over many years before clinical symptoms appear, providing the opportunity to develop therapy that could slow or stop disease progression well before any clinical manifestation develops.

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