bims-curels 2024-09-01 papers

Issue of 2024–09–01
three papers selected by
Cure Mito Foundation

Cureus. 2024 Jul;16(7): e65239

A DNA Polymerase Subunit Gamma (POLG) Mutation Imposing a Difficult Differential Diagnosis of Hepatic Encephalopathy in a Newborn: A Case Report.

Ithamar Cheyne, Bartosz Boryszewski, Wyven Chang, Małgorzata Mikaszewska-Sokolewicz.

Hepatic encephalopathy (HE) is a condition connected with neuropsychiatric alteration during hepatic failure. The differential diagnosis of HE is challenging due to overlapping symptoms with other conditions. Polymerase subunit gamma (POLG) is a mitochondrial gene, and an infant POLG mutation can manifest with severe and progressive hepatic failure and encephalopathy, imposing a difficult differential diagnosis due to similarities to other conditions. The lack of curative treatment leads to a poor prognosis. An 11-month-old boy was admitted to the intensive care unit (ICU) due to altered consciousness and increasing edema due to acute hepatic failure of unknown etiology. After extensive multidisciplinary discussions and a lack of response to treatment for more than three weeks, a mitochondrial disease was suspected, and a genetic test was taken. The patient's condition continued to deteriorate. The patient died on the 25th day of hospitalization in the ICU. After death, a genetic test confirmed a rare POLG mutation NM_002693.3(POLG):c.3104+2T>A (Variation ID: 422378 Accession: VCV000422378.8). We suggest that a screen test for POLG mutations be considered early in the diagnostic process and that clinicians consider mitochondrial genetic mutations, such as POLG mutations, more often. This article is the first to describe a patient with this specific mutation.

Keywords: case report; differential diagnosis; genetic predisposition to disease; hepatic encephalopathy; polg

DOI: https://doi.org/10.7759/cureus.65239

Biomedicines. 2024 Aug 15. pii: 1868. [Epub ahead of print]12(8):

Variability of Mitochondrial DNA Heteroplasmy: Association with Asymptomatic Carotid Atherosclerosis.

Margarita A Sazonova, Tatiana V Kirichenko, Anastasia I Ryzhkova, Marina D Sazonova, Natalya A Doroschuk, Andrey V Omelchenko, Nikita G Nikiforov, Yulia I Ragino, Anton Yu Postnov.

Background and Objectives: Atherosclerosis is one of the main reasons for cardiovascular disease development. This study aimed to analyze the association of mtDNA mutations and atherosclerotic plaques in carotid arteries of patients with atherosclerosis and conditionally healthy study participants from the Novosibirsk region. Methods: PCR fragments of DNA containing the regions of 10 investigated mtDNA mutations were pyrosequenced. The heteroplasmy levels of mtDNA mutations were analyzed using a quantitative method based on pyrosequencing technology developed by M. A. Sazonova and colleagues. Results: In the analysis of samples of patients with atherosclerotic plaques of the carotid arteries and conditionally healthy study participants from the Novosibirsk region, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected. A west-east gradient was found in the distribution of the mtDNA mutations m.5178C>A, m.3256C>T, m.652insG, and m.13513G>A. Conclusions: Therefore, four proatherogenic mutations in the mitochondrial genome (m.5178C>A, m.652delG, m.12315G>A, and m.3256C>T) and three antiatherogenic mutations in mtDNA (m.13513G>A, m.652insG, and m.14846G>A) were detected in patients with atherosclerotic plaques in their carotid arteries from the Novosibirsk region.

Keywords: atherosclerosis; atherosclerotic plaque; cardiovascular risk; gene; heteroplasmy level; mitochondrion; mutation; pyrosequencing; total mutational burden

DOI: https://doi.org/10.3390/biomedicines12081868