A neonate with ornithine aminotransferase deficiency; insights on the hyperammonemia-associated biochemical phenotype of gyrate atrophy

Kaczmarczyk, Aneta; Baker, Mark; Diddle, Julianna; Yuzyuk, Tatiana; Valle, David; Lindstrom, Kristin

doi:10.1016/j.ymgmr.2022.100857

Cited by 3 publications

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Multimodal imaging and genetic screening in Mexican patients with Gyrate atrophy: identification of novel OAT pathogenic variants

Díazceballos-García,

Matsui,

Chairez Miranda

et al. 2024

Int Ophthalmol

View full text Add to dashboard Cite

Purpose Description of retinal phenotype by structural and functional testing, ornithine plasma levels and mutational data of OAT gene in patients with Gyrate Atrophy (GA) . Methods Ophthalmologic examination, fundus photography (CFP), autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann perimetry (GP), full-field electroretinogram (ffERG) and chromatic perimetry (CP) testing were performed. Ornithine plasma levels were measured. Sanger sequencing mutational analysis of the coding exons and exon–intron junctions of the OAT gene were analyzed. Results Twelve eyes of seven Mexican patients with GA were included. CFF showed peripheric patches of chorioretinal atrophy; FAF revealed peripheric oval areas of hypoautofluorescence; SD-OCT exhibited outer retinal tubulations in 58%, cystoid macular edema in 50%, epiretinal membrane in 42%, foveoschisis and staphyloma in 17%, and hyperreflective deposits in 100% of the eyes; GP showed constricted visual fields in 100% of the eyes; ffERG revealed preserved photopic response in 17% and preserved scotopic response in 17% of the eyes; CP exposed a deficit in generalized response of rods and cones in 100% of the eyes. Mean ornithine plasma levels were 509.5 µmol/L. One patient with genetic confirmation of GA had normal ornithine plasma levels (48 µmol/L). Molecular findings in OAT gene detected two novel pathogenic variants: c.796 C > T (p.Gln266*) and c.721_722dupCC (p.Asp242ArgfsTer6). Conclusion This study provides new information regarding functional and structural diagnosis in patients with GA, expands the understanding of retinal phenotype in patients with GA, reports two novel mutations and presents the first case of GA confirmed by genetic testing with normal ornithine levels.

show abstract

Multimodal imaging and genetic screening in Mexican patients with Gyrate atrophy: identification of novel OAT pathogenic variants

Díazceballos-García,

Matsui,

Chairez Miranda

et al. 2024

Int Ophthalmol

View full text Add to dashboard Cite

show abstract

Advancing precision care in pregnancy through an actionable fetal findings list

Cohen,

Duyzend,

Adelson

et al. 2024

Preprint

View full text Add to dashboard Cite

The use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade. Fetal GS also offers an opportunity to identify incidental genomic variants that are unrelated to the fetal phenotype, but may be relevant to fetal and newborn health. There are currently no guidelines for reporting incidental findings from fetal GS. In the United States, GS for adults and children is recommended to include a list of "secondary findings" genes (ACMG SF v3.2) that are associated with disorders for which surveillance or treatment can reduce morbidity and mortality. The genes on ACMG SF v3.2 predominantly cause adult-onset disorders. Importantly, many genetic disorders with fetal and infantile onset are actionable as well. A proposed solution is to create a "fetal actionable findings list," which can be offered to pregnant patients undergoing fetal GS or eventually, as a standalone cell-free fetal DNA screening test. In this integrative review, we propose criteria for an actionable fetal findings list, then identify genetic disorders with clinically available or emerging fetal therapies, and those for which clinical detection in the first week of life might lead to improved outcomes. Finally, we synthesize the potential benefits, limitations, and risks of an actionable fetal findings list.

show abstract

Molecular Mechanisms Underlying Therapeutic Action of Vitamin B6

Zagubnaya

Nartsissov

2023

Farm. farmakol. (Pâtigorsk)

View full text Add to dashboard Cite

The aim of the study was to analyze the molecular mechanisms that determine the possibility of using vitamin B6 in clinical practice for the correction of various pathological conditions.Materials and methods. Information retrieval (Scopus, PubMed) and library (eLibrary) databases were used as research tools. In some cases, the ResearchGate application was used for a semantic search. The analysis and generalization of the scientific literature on the topic of research, covering the period from 1989 to the present, has been carried out in the work.Results. It has been shown that all chemical forms of vitamin B6 are able to penetrate the membranes of most cells by free diffusion, while forming phosphorylated forms inside. Pyridoxal phosphate is a biologically important metabolite that is directly involved as a cofactor in a variety of intracellular reactions. Requirements for this cofactor depend on the age, sex and condition of the patient. Pregnancy and lactation play a special role in the consumption of vitamin B6. In most cases, a balanced diet will provide an acceptable level of this vitamin. At the same time, its deficiency leads to the development of a number of pathological conditions, including neurodegenerative diseases, inflammations and diabetes. Negative manifestations from the central nervous system are also possible with an excessive consumption of B6.Conclusion. Replenishment of the vitamin B6 level in case of its identified deficiency is a necessary condition for the successful treatment of the central nervous system diseases, diabetes and correction of patients’ immune status. At the same time, it is necessary to observe a balanced intake of this cofactor in order to avoid negative effects on metabolism in case of its excess.

show abstract

A neonate with ornithine aminotransferase deficiency; insights on the hyperammonemia-associated biochemical phenotype of gyrate atrophy

Cited by 3 publications

References 23 publications

Multimodal imaging and genetic screening in Mexican patients with Gyrate atrophy: identification of novel OAT pathogenic variants

Multimodal imaging and genetic screening in Mexican patients with Gyrate atrophy: identification of novel OAT pathogenic variants

Advancing precision care in pregnancy through an actionable fetal findings list

Molecular Mechanisms Underlying Therapeutic Action of Vitamin B6

Contact Info

Product

Resources

About