MİTOKONDRİYAL YAĞ ASİDİ OKSİDASYON BOZUKLUĞU OLAN 72 HASTANIN GERİYE DÖNÜK DEĞERLENDİRİLMESİ: 32 YILLIK DENEYİM

Abstract

Retrospective Evaluation of 72 Patients with Mitochondrial Fatty Acid Oxidation Disorders: 32 Years of Experience. Hacettepe University Faculty of Medicine, Residency Thesis in Pediatric, Ankara, 2024. In mammals, fatty acid oxidation (FAO) is an important source of energy production during periods of high energy requirement, such as prolonged fasting and exercise. The brain uses ketone bodies as an energy source during fasting. Therefore, the production rate of ketone bodies should increase during fasting and prolonged intense exercise. Ketone bodies are produced in the liver mainly from acetyl-Coenzyme A (acetyl-CoA) and acetoacetyl-CoA produced by β-oxidation of fatty acids, and to a lesser extent from some amino acids. To supply these substrates during fasting periods, fatty acids undergo mitochondrial beta-oxidation in liver, heart muscle and skeletal muscle. In mitochonodrial FAO disorders, fats released from adipose tissue cannot be oxidized and accumulate in organs such as skeletal and cardiac muscle and liver, impairing their function. In this study, we retrospectively reviewed the patients who were followed up with a diagnosis of fatty acid oxidation disorder in the Department of Metabolism at Hacettepe University İhsan Doğramacı Children's Hospital, one of the most experienced metabolic disease centers in our country. The study included 72 patients diagnosed by family screening or newborn screening while asymptomatic, or after becoming symptomatic between 1988 and 2020. Three patients were diagnosed by newborn screening and six patients were diagnosed before the onset of the disease due to the presence of fatty acid oxidation disorder in the sibling. Parental consanguinity was present in 61.9% of the patients. Symptomatic patients had complaints related to the gastrointestinal system and muscle tissue at first presentation. Liver findings were the most common clinical manifestation. Of the 72 patients constituting the study group, Assuming the presence of the same genetic disorder in siblings with clinically and metabolically identical disease presentation, the diagnosis was confirmed by molecular genetic analysis in 61 patients, and by enzyme studies in cultured fibroblasts in three patients. Eight patients were diagnosed based on clinical and biochemical findings. One patient had carnitine palmitoyl transferase 1 (CPT1) deficiency, six had carnitine palmitoyl transferase 2 (CPT2) deficiency, four had carnitine-acyl carnitine translocase (CACT) deficiency, twelve had primary carnitine deficiency (PCD); two patients were diagnosed with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, five with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency and eight with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. The largest group was the multiple acyl-CoA dehydrogenase (MAD) deficiency group with 34 patients. Most diagnostic delays were seen in patients with multiple acyl-CoA dehydrogenase and carnitine palmitoyl transferase 2 deficiencies. Since this study reflects the general characteristics and follow-up of patients diagnosed with fatty acid oxidation disorders in our country, it is thought to be a resource for improving the diagnosis and follow-up processes of patients.