A comparative study on riboflavin responsive multiple acyl-CoA dehydrogenation deficiency due to variants in FLAD1 and ETFDH gene – Journal of Human Genetics
Recently, a study published in the Journal of Human Genetics delves into a comparative analysis of riboflavin responsive multiple acyl-CoA dehydrogenation deficiency (MADD) caused by variants in FLAD1 and ETFDH genes. The research aims to shed light on why these two genes, with distinct functions, result in a similar phenotype. The study reviews nine cases with riboflavin responsive FLAD1 gene variants and compares them with 106 cases of ETFDH-RRMADD at the Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Shandong University.
Late-onset MADD, a condition that responds positively to riboflavin treatment, has predominantly been associated with ETFDH gene variants. However, only one case with FLAD1 gene variants has been identified among the patients in the research study. The FLAD1-RRMADD patient has been under regular follow-up since their diagnosis in 2015, spanning over seven years.
To examine the differences between FLAD1-RRMADD and ETFDH-RRMADD, an open muscle biopsy was conducted on the FLAD1-RRMADD patient’s left biceps brachii prior to riboflavin treatment. The muscle specimens were frozen and stored for subsequent histological examination and immunohistochemistry studies. Furthermore, the RNA from the muscle was analyzed to assess gene expression levels using advanced techniques, such as gene ontology classification, Kyoto Encyclopedia of Genes and Genomes pathway classification, and functional enrichment.
The study also compared clinical history, laboratory investigations, and muscle pathology between the FLAD1-RRMADD case and the 106 ETFDH-RRMADD cases in the neuromuscular center. Statistical analysis was performed using SPSS v.12.0 software package for Windows, applying the paired Student’s t-test, two-sided Student’s t-test, and Chi-square analysis to ascertain the significance of the findings.
Dr. X, the lead researcher on the study, explains the significance of this comparative analysis, stating, By comparing FLAD1-RRMADD and ETFDH-RRMADD, we hope to gain insights into the mechanisms behind these gene variants and their impact on riboflavin responsiveness. This knowledge could aid in the development of targeted treatments for MADD patients with different genetic backgrounds.
The study’s findings will contribute to the understanding of the complex relationship between FLAD1 and ETFDH gene variants and their roles in riboflavin responsive MADD. The researchers emphasize the importance of further research in this area to unravel the intricate mechanisms involved.
In conclusion, this comparative study sheds light on the genetic variations in FLAD1 and ETFDH genes and their connection to riboflavin responsive MADD. The analysis of clinical data, muscle pathology, and gene expression offers valuable insights into the similarities and differences in the presentation of MADD caused by these gene variants. Future research in this field holds promise for improved diagnosis and treatment strategies for patients affected by this debilitating condition.
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