Gyrate Atrophy of the Choroid and Retina: A Review

2021 ◽  
pp. 112067212110673
Author(s):  
Ayman G. Elnahry ◽  
Gehad A. Elnahry
Keyword(s):  
Amino Acid ◽  
Multimodal Imaging ◽  
Autosomal Recessive ◽  
Treatment Options ◽  
Genetic Condition ◽  
Gyrate Atrophy ◽  
Ophthalmic Manifestations ◽  
Body Tissues ◽  
Dietary Modifications ◽  
Visual Field Constriction

Gyrate atrophy (GA) of the choroid and retina is a rare autosomal recessive genetic condition characterized by elevation of the plasma level of the amino acid ornithine due to deficiency of the enzyme ornithine ketoacid aminotransferase. Accumulation of ornithine occurs in various body tissues but leads primarily to characteristic ophthalmic manifestations including myopia, cataract, progressive chorioretinal atrophy, and macular changes. Patients usually present with night blindness that starts in the first decade of life followed by visual field constriction and eventually diminution of the central visual acuity and blindness. The condition has been reported worldwide and its differential diagnosis is broad and includes choroideremia and retinitis pigmentosa. Treatment currently depends on life-long dietary modifications including restriction of the amino acid arginine in diet. This article describes in detail the pathogenesis, clinical features, multimodal imaging findings, and treatment options for GA of the choroid and retina and its complications.

scholarly journals McArdle disease and pregnancy: A case report and scoping review of pregnancy outcomes

2021 ◽  
pp. 1753495X2110161
Author(s):  
Christopher M Nash ◽  
Nabha Shetty ◽  
Ashley Miller ◽  
Kyle McCoy
Keyword(s):  
Scoping Review ◽  
Pregnancy Outcomes ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Glycogen Metabolism ◽  
Limited Data ◽  
Genetic Condition ◽  
Second Stage ◽  
Mcardle Disease ◽  
Pregnancy And Delivery

McArdle disease is an autosomal recessive disorder affecting skeletal muscle glycogen metabolism. Limited data are available regarding pregnancy outcomes with this genetic condition. We present a recent case of a woman with McArdle disease, along with a scoping review of all published literature regarding pregnancy and delivery outcomes for women with McArdle disease. A total of 35 cases are summarised. Overall, pregnancy does not worsen or increase the risk for disease flare. Women can successfully deliver vaginally, with consideration of an assisted second stage recommended to reduce the risk of postpartum rhabdomyolysis.

Multimodal imaging of autosomal recessive cornea plana associated with hard mature and polar cataract

2021 ◽  
Vol 1 (3) ◽  
pp. 393
Author(s):  
VijayalakshmiA Senthilkumar ◽  
VidyaS Raja ◽  
Kavya Kondepati ◽  
TechiD Tara
Keyword(s):  
Multimodal Imaging ◽  
Autosomal Recessive

Diagnostic value of a combination of next-generation sequencing, chorioretinal imaging and metabolic analysis: lessons from a consanguineous Chinese family with gyrate atrophy of the choroid and retina stemming from a novel OAT variant

2018 ◽  
Vol 103 (3) ◽  
pp. 428-435 ◽  
Author(s):  
Junting Huang ◽  
Jiewen Fu ◽  
Shangyi Fu ◽  
Lisha Yang ◽  
Kailai Nie ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Low Income ◽  
Autosomal Recessive ◽  
Diagnostic Value ◽  
Consanguineous Marriage ◽  
Chinese Family ◽  
Next Generation ◽  
Gyrate Atrophy ◽  
Metabolic Analysis ◽  
Generation Sequencing

Background/AimGyrate atrophy of the choroid and retina (GACR) is an extremely rare autosomal recessive inherited disorder characterised by progressive vision loss. To identify the disease-causing gene in a consanguineous Chinese pedigree with GACR, we aimed to accurately diagnose patients with GACR through a combination of next-generation sequencing (NGS) genetic diagnosis, clinical imaging and amino acid metabolic analysis.MethodsA consanguineous Chinese pedigree with GACR, including two patients, was recruited and a comprehensive ophthalmological evaluation was performed. DNA was extracted from a proband and her family members, and the sample from the proband was analysed using targeted NGS. Variants ‎detected by NGS were confirmed by Sanger sequencing and subjected to segregation analysis. Tandem mass spectrometry (MS/MS) was subsequently performed for metabolic assessment.ResultsWe identified a ‎novel, deleterious, homologous ornithine aminotransferase (OAT) variant, c.G248A: p.S83N, which contributes to ‎the progression of GACR in patients. Our results showed that the p.S83N autosomal recessive ‎variant of OAT is most likely ‎pathogenic, with changes in protein stability drastically decreasing functionality. MS/MS verified that ornithine levels in patients were significantly elevated.ConclusionsRecruitment of a third-degree first cousin consanguineous marriage family with GACR allowed us to identify a novel pathogenicOATvariant in the Chinese population, broadening the mutation spectrum. Our findings reported the diagnostic value of a combination of NGS, retinal imaging and metabolic analysis of consanguineous marriage pedigrees in low-income/middle-income and low-incidence countries, including China, and may help to guide accurate diagnosis and ‎treatment of this disease.

scholarly journals GREENBERG'S DYSPLASIA- A RARE GENETIC CONDITION

2020 ◽  
pp. 16-17
Author(s):  
Sundari S ◽  
Javeri Aarti Harish
Keyword(s):  
Skeletal Dysplasia ◽  
Autosomal Recessive ◽  
Ectopic Calcification ◽  
Genetic Condition ◽  
Lamin B ◽  
Lamin B Receptor

Greenberg’s Dysplasia, also known as Hydrops-Ectopic calcification-Moth-Eaten (HEM) Skeletal Dysplasia, is a rare autosomal recessive osteochondrodysplasia, caused by mutation in the Lamin B Receptor (LBR) Gene, on chromosome 1q42.

Atypical Presentation of Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency with Developmental Epileptic Encephalopathy

2021 ◽  
Author(s):  
Francesca Marchese ◽  
Elena Faedo ◽  
Maria Stella Vari ◽  
Patrizia Bergonzini ◽  
Michele Iacomino ◽  
...  
Keyword(s):  
Amino Acid ◽  
Autosomal Recessive ◽  
Epileptic Encephalopathy ◽  
Dopa Decarboxylase ◽  
Acid Decarboxylase ◽  
Homozygous Mutation ◽  
Amino Acid Decarboxylase ◽  
Pathogenic Variants ◽  
Neurological Features ◽  
Decarboxylase Deficiency

AbstractAromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive metabolic disorder resulting from disease-causing pathogenic variants of the dopa decarboxylase (DDC) gene. The neurological features of AADC deficiency include early-onset hypotonia, oculogyric crises, ptosis, dystonia, hypokinesia, impaired development, and autonomic dysfunction. We report a patient with genetically confirmed AADC deficiency presenting with developmental epileptic encephalopathy (DEE). We report a boy with severe intractable epileptic spasms and DEE. The patient was evaluated for cognitive and neurologic impairment. Exome sequencing revealed a homozygous mutation (NM_000790.4:c.121C > A; p.Leu41Met) in the DDC gene. This case expands the clinical spectrum of AADC deficiency and strengthens the association between dopa decarboxylase deficiency and epilepsy. Additional studies are warranted to clarify the mechanisms linking dopa decarboxylase dysfunction to DEE.

scholarly journals Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1021
Author(s):  
Amjad Khan ◽  
Zhichao Miao ◽  
Muhammad Umair ◽  
Amir Ullah ◽  
Mohammad A. Alshabeeb ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Secondary Structure ◽  
Homology Modeling ◽  
Exome Sequencing ◽  
In Silico ◽  
Brain Function ◽  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Wild Type ◽  
Genetic Condition

Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal recessive ID: NDST1 (c.1966G>A; p.Asp656Asn) and METTL23 (c.310T>C; p.Phe104Leu). The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the secondary structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic NDST1 and METTL23 variants in two cases of autosomal recessive ID further highlight the importance of these genes in proper brain function and development.

scholarly journals OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Christopher Fröhlich ◽  
Vidar Sørum ◽  
Ane Molden Thomassen ◽  
Pål Jarle Johnsen ◽  
Hanna-Kirsti S. Leiros ◽  
...  
Keyword(s):  
Amino Acid ◽  
Inhibitory Activity ◽  
Treatment Options ◽  
Inhibitory Effect ◽  
Amino Acid Substitutions ◽  
Gram Negative ◽  
Content Type ◽  
Mortality And Morbidity ◽  
Trade Offs ◽  
Collateral Effects

ABSTRACTInfections due to carbapenemase-producing Gram-negative pathogens are associated with limited treatment options and consequently lead to increased mortality and morbidity. In response, combinations of existing β-lactams and novel β-lactamase inhibitors, such as ceftazidime-avibactam (CAZ-AVI), have been developed as alternative treatment options. To understand the development of resistance and evolutionary trajectories under CAZ-AVI exposure, we studied the effects of ceftazidime (CAZ) and CAZ-AVI on the carbapenemase OXA-48 and the epidemic OXA-48 plasmid inEscherichia coli. Exposure of CAZ and CAZ-AVI resulted in single (P68A) and double (P68A,Y211S) amino acid substitutions in OXA-48, respectively. The antimicrobial susceptibility data and enzyme kinetics showed that the P68A substitution was responsible for an increased activity toward CAZ, whereas P68A,Y211S led to a decrease in the inhibitory activity of AVI. X-ray crystallography and molecular modeling of the mutants demonstrated increased flexibility within the active site, which could explain the elevated CAZ hydrolysis and reduced inhibitory activity of AVI. Interestingly, these substitutions resulted in collateral effects compromising the activity of OXA-48 toward carbapenems and penicillins. Moreover, exposure to CAZ-AVI selected for mutations within the OXA-48-encoding plasmid that severely reduced fitness in the absence of antimicrobial selection. These evolutionary trade-offs may contribute to limit the evolution of OXA-48-mediated CAZ and CAZ-AVI resistance, as well as potentially resensitize isolates toward other therapeutic alternatives.IMPORTANCEThe recent introduction of novel β-lactam/β-lactamase inhibitor combinations like ceftazidime-avibactam has increased our ability to treat infections caused by multidrug-resistant Gram-negative bacteria, including carbapenemase-producingEnterobacterales. However, the increasing number of cases of reported resistance to ceftazidime-avibactam is a concern. OXA-48 is a carbapenemase that has no significant effect on ceftazidime, but is inhibited by avibactam. Since isolates with OXA-48 frequently harbor extended-spectrum β-lactamases that are inhibited by avibactam, it is likely that ceftazidime-avibactam will be used to treat infections caused by OXA-48-producingEnterobacterales.Our data show that exposure to ceftazidime-avibactam can lead to changes in OXA-48, resulting in increased ability to hydrolyze ceftazidime and withstand the inhibitory effect of avibactam. Thus, resistance toward ceftazidime-avibactam among OXA-48-producingEnterobacteralesshould be monitored. Interestingly, the compromising effect of the amino acid substitutions in OXA-48 on other β-lactams and the effect of ceftazidime-avibactam exposure on the epidemic OXA-48 plasmid indicate that the evolution of ceftazidime-avibactam resistance comes with collateral effects.

scholarly journals Amino Acid Changes in the Mouse Mutant Dystonia Musculorum Similar to Those in Friedreich’s Ataxia

1982 ◽  
Vol 9 (2) ◽  
pp. 185-188 ◽  
Author(s):  
A. Messer
Keyword(s):  
Amino Acid ◽  
Experimental Model ◽  
Neurological Disorder ◽  
Autosomal Recessive ◽  
Red Nucleus ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Mouse Mutant ◽  
Sensory Afferents ◽  
Recessive Mutant

SUMMARY:An autosomal recessive mutant strain of mouse with a progressive neurological disorder is described. Histopathology is dramatic in the sensory afferents and in the red nucleus. In the cerebellar vermis the concentrations of glutamate, aspartate, glycine and GABA are significantly reduced, and in the cerebellar hemispheres the taurine/glutamate ratio is elevated. These mice may provide a useful experimental model of Friedreich’s ataxia.

Diagnosis and treatment of peripheral exudative haemorrhagic chorioretinopathy

2019 ◽  
Vol 104 (6) ◽  
pp. 874-878 ◽  
Author(s):  
Sarah Vandefonteyne ◽  
Jean-Pierre Caujolle ◽  
Laurence Rosier ◽  
John Conrath ◽  
Gabriel Quentel ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Multimodal Imaging ◽  
Chart Review ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Choroidal Melanoma ◽  
Endothelial Growth Factor

PurposePeripheral exudative haemorrhagic chorioretinopathy (PEHCR) is a rare disorder that is often misdiagnosed. The aim of this study was to better characterise PEHCR and to assess treatment options.Material and methodsRetrospective multicentric chart review.ResultsOf 84 eyes (69 patients) with PEHCR referred between 2005 and 2017, the most common referral diagnosis was choroidal melanoma (41.3%). Bilateral involvement was found in 21.7% of cases. Haemorrhagic retinal pigment epithelium detachment was the most common peripheral lesion (53.6%). Maculopathy was associated with peripheral lesions in 65.8% of cases. PEHCR lesions were mostly heterogeneous (58.8%) on B-scan ultrasonography. Choroidal neovascularisation was found in 10 eyes (26.3%) out of 38 eyes that underwent fluorescein angiography. Polyps were observed in 14 eyes (58.3%) out of 24 eyes that underwent indocyanine green angiography. Fifty-one eyes were treated (62.2%). Intravitreal injections (IVTI) of antivascular endothelial growth factor (VEGF) were the most used treatment (36.6%) before laser photocoagulation, photodynamic therapy, vitrectomy and cryotherapy. Only vitrectomy improved visual acuity. Most lesions (65.6%) regressed at the last follow-up visit.ConclusionIn case of PEHCR, multimodal imaging is useful to avoid misdiagnosis, to characterise PEHCR lesions and to guide treatment strategies. Regression of PEHCR lesions was observed in two-thirds of the patients. Vitrectomy improved visual acuity. More than a third of patients underwent anti-VEGF IVTI. Further studies are needed to assess IVTI’s efficacy.

Recurrent Dystonic Crisis and Rhabdomyolysis Treated with Dantrolene in Two Patients with Aromatic L-Amino Acid Decarboxylase Deficiency

2020 ◽  
Vol 51 (03) ◽  
pp. 229-232
Author(s):  
J. Micallef ◽  
S. Stockler-Ipsiroglu ◽  
C.D. van Karnebeek ◽  
R. Salvarinova-Zivkovic ◽  
G. Horvath
Keyword(s):  
Amino Acid ◽  
Inborn Error ◽  
Autosomal Recessive ◽  
Global Developmental Delay ◽  
Acid Decarboxylase ◽  
First Year ◽  
Amino Acid Decarboxylase ◽  
History Of ◽  
First Year Of Life ◽  
Decarboxylase Deficiency

AbstractAromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive inborn error of metabolism in which several neurotransmitters including serotonin, dopamine, norepinephrine and epinephrine are deficient. Symptoms typically appear in the first year of life and include oculogyric crises and dystonia, hypotonia, and global developmental delay. Dystonia is of particular concern as a dystonic storm can ensue leading to rhabdomyolysis. Rhabdomyolysis can become life-threating and therefore its recognition and prompt management is of significant importance. Here we present two cases of patients with AADC deficiency and a history of dystonic crisis causing rhabdomyolysis. We hypothesize that in addition to the hypodopaminergic, a hypercholinergic state is contributing to the pathophysiology of dystonia in AADC deficiency, as well as to the associated rhabdomyolysis. We were able to prevent rhabdomyolysis in both patients with using Dantrolene and we suggest using a trial of this medication in cases of sustained dystonic crisis in AADC deficiency patients.

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