Researchers from Italy published a new article about hypoglycemia metabolic gene panel testing and how this approach can help guide the timely diagnosis and specific treatment of different disorders that impair glucose homeostasis, including long chain fatty acid oxidation disorders (LCFAOD).
“Historically, genetic analysis consisted of highly detailed molecular testing of nominated single genes,” first author Arianna Maiorana, MD, PhD, and the coauthors of the article wrote. “However, more recently, the genetic heterogeneity of these conditions imposed to perform extensive molecular testing within a useful timeframe via new generation sequencing technology.”
Based on biochemical and clinical phenotypes, molecular analysis can focus on gene clusters involved in specific pathways. This approach can allow the identification of disease-causing variants that may have been thought of as variants of uncertain significance or even the discovery of new genes associated with the disease.
Read more about the etiology of LCFAOD
The authors also said that this approach can help better characterize a disease phenotypically in case pathogenic variants give rise to unexpected clinical pictures.
“Multidisciplinary input and collaboration are increasingly key for addressing the analysis and interpreting the significance of the genetic results, allowing rapidly their translation from bench to bedside,” they wrote.
LCFAOD is one of many conditions that can lead to impaired glucose homeostasis. It is caused by inborn errors of metabolism involving fatty acid oxidation. Phenotypically, the disease is characterized by hypoketotic hypoglycemia induced by fasting or stress. Because long-chain fatty acids are mainly used by the heart and skeletal muscles, symptoms of the disease include rhabdomyolysis, cardiomyopathy, and arrhythmias.
There are 6 types of LCFAODs, all caused by a mutation in a different gene. These are carnitine palmitoyltransferase 1 and 2 deficiencies, carnitine-acylcarnitine translocase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxy-acyl-CoA dehydrogenase deficiency, and trifunctional protein deficiency.
Maiorana A, Lepri FR, Novelli A, Dionisi-Vici C. Hypoglycaemia metabolic gene panel testing. Front Endocrinol (Lausanne). 2022;13:826167. doi:10.3389/fendo.2022.826167