Objective: To evaluate the clinical, radiological, and biochemical features of glutaric aciduria Type 1 (GA1) patients identified through urine organic acid testing at a biochemical genetics laboratory (BGL) in Pakistan.
Study Design: Observational study. Place and Duration of the Study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, Pakistan, from January 2013 to December 2022.
Methodology: Medical charts and urine organic acid (UOA) chromatograms of the patients presenting at the BGL from January 2013 to December 2022 were reviewed. Brain imaging was obtained where available. Variables were noted as per the objective and descriptive statistics were obtained.
Results: GA1 was found in 64 (0.4%) patients out of a total of 16,094 UOA requests for high-risk screening cases. The age of diagnosis ranged between one month and three years. The brain MRI findings revealed characteristic abnormalities such as cerebral atrophy, expanded CSF spaces, white matter abnormalities, and a distinct bat wings appearance, in cohesion with the results of biochemical testing.
Conclusion: Sixty-four cases of GA1 from a single centre indicate a high frequency of the disorder in Pakistan. Late diagnosis emphasises the need for increased clinical awareness and preferably newborn screening to ensure optimal outcomes.
Key Words: Glutaric aciduria Type 1 (GA1), Brain imaging, UOA analysis, Glutaryl-CoA dehydrogenase (GCDH), Pakistan.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.29271/jcpsp.2024.06.646 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Digital-Tier Strategy Improves Newborn Screening for Glutaric Aciduria Type 1.
Int J Neonatal Screen
December 2024
Engineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, 69120 Heidelberg, Germany.
Glutaric aciduria type 1 (GA1) is a rare inherited metabolic disease increasingly included in newborn screening (NBS) programs worldwide. Because of the broad biochemical spectrum of individuals with GA1 and the lack of reliable second-tier strategies, NBS for GA1 is still confronted with a high rate of false positives. In this study, we aim to increase the specificity of NBS for GA1 and, hence, to reduce the rate of false positives through machine learning methods.
View Article and Find Full Text PDFA Rare Presentation of Glutaric Aciduria Type 1 in an Adult.
Neurol India
November 2024
Department of Neurology, Ramaiah Medical College, Bengaluru, Karnataka, India.
Restricting lysine normalizes toxic catabolites associated with ALDH7A1 deficiency in cells and mice.
Cell Rep
December 2024
Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; British Columbia Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada. Electronic address:
Lysine metabolism converges at α-aminoadipic semialdehyde dehydrogenase (ALDH7A1). Rare loss-of-function mutations in ALDH7A1 cause a toxic accumulation of lysine catabolites, including piperideine-6-carboxylate (P6C), that are thought to cause fatal seizures in children unless strictly managed with dietary lysine reduction. In this study, we perform metabolomics and expression analysis of tissues from Aldh7a1-deficient mice, which reveal tissue-specific differences in lysine metabolism and other metabolic pathways.
View Article and Find Full Text PDFGlutaric aciduria type 1: Insights into diagnosis and neurogenetic outcomes.
Eur J Pediatr
December 2024
Department of Pediatric Metabolism and Nutrition, Medical Faculty, Ege University, Izmir, 35040, Turkey.
Unlabelled: Glutaric aciduria type 1 (GA1) is a rare metabolic disorder characterized by a deficiency in the enzyme glutaryl-CoA dehydrogenase. This study aims to present the clinical, biochemical, genetic, and neuroimaging findings of GA1 patients, emphasizing the importance of early detection and the potential benefits of incorporating GA1 into NBS programs. The demographic, clinical, and laboratory findings of GA1 patients were reviewed retrospectively.
View Article and Find Full Text PDFProtective effects of the PPAR agonist bezafibrate against disruption of redox and energy homeostasis, neuronal death, astroglial reactivity, and neuroinflammation induced in vivo by D-2-hydroxyglutaric acid in rat brain.
Eur J Pharmacol
January 2025
Postgraduation Program in Biological Sciences: Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, 90035-007, Brazil. Electronic address:
The biochemical hallmark of D-2-hydroxyglutaric aciduria is brain accumulation of D-2-hydroxyglutaric acid (D2HG). Patients present predominantly neurological manifestations, whose pathogenesis is still unknown. Thus, we examined the impact of elevated brain levels of D2HG, induced by intracerebral injection of this metabolite in juvenile rats, on redox and mitochondrial homeostasis and histochemical landmarks in the cerebral cortex.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!