Management and outcome in 75 individuals with long‐chain fatty acid oxidation defects: results from a workshop

Abstract

At present, long-chain fatty acid oxidation (FAO) defects are diagnosed in a number of countries by newborn screening using tandem mass spectrometry. In the majority of cases, affected newborns are asymptomatic at time of diagnosis and acute clinical presentations can be avoided by early preventive measures. Because evidence-based studies on management of long-chain FAO defects are lacking, we carried out a retrospective analysis of 75 patients from 18 metabolic centres in Germany, Switzerland, Austria and the Netherlands with special regard to treatment and disease outcome. Dietary treatment is effective in many patients and can prevent acute metabolic derangements and prevent or reverse severe long-term complications such as cardiomyopathy. However, 38% of patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency had intermittent muscle weakness and pain despite adhering to therapy. Seventy-six per cent of patients with disorders of the mitochondrial trifunctional protein (TFP)-complex including long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, had long-term myopathic symptoms. Of these, 21% had irreversible peripheral neuropathy and 43% had retinopathy. The main principle of treatment was a fat-reduced and fat-modified diet. Fat restriction differed among patients with different enzyme defects and was strictest in disorders of the TFP-complex. Patients with a medium-chain fat-based diet received supplementation of essential long-chain fatty acids. l-Carnitine was supplemented in about half of the patients, but in none of the patients with VLCAD deficiency identified by newborn screening. In summary, in this cohort the treatment regimen was adapted to the severity of the underlying enzyme defect and thus differed among the group of long-chain FAO defects.

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

“…Impaired transfer of electrons affects multiple dehydrogenation reactions and is thus termed multiple acylCoA dehydrogenase (MAD) deficiency. FAO disorders can present with life-threatening symptoms, such as hypoketotic hypoglycemia, Reye-like syndrome in infants (Brivet et al 1999;Baruteau et al 2009;Spiekerkoetter 2010), acute encephalopathy (Gregersen et al 2001;Spiekerkoetter 2010), cardiomyopathy (Bonnet et al 1999;Spiekerkoetter et al 2009a), myolysis (Spiekerkoetter et al 2009a;van Adel and Tarnopolsky 2009), and liver dysfunction (Clayton 2003). Currently more than 15 distinct FAO disorders have been elucidated based on enzymatic and/or molecular analyses (Gregersen et al 2008).…”

Long-chain Acyl-CoA Dehydrogenase Deficiency as a Cause of Pulmonary Surfactant Dysfunction

“…VLCAD expression predominates in tissues that are known to rely upon fatty acids for energy such as liver, heart, and muscle. Correspondingly, VLCAD deficiency causes life-threatening metabolic decompensation, cardiomyopathy, and muscle weakness (6,7). ACAD9 is also expressed in muscle and heart and is the only ACAD enzyme expressed at high levels in the brain and central nervous system (4).…”

Growth in Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

“…The diagnosis is usually established within the first year of life, often when nightly feedings are weaned (Saudubray et al 1999;Tyni et al 1997;Spiekerkoetter et al 2009a). Some patients present with acute symptoms such as coma, cardiac arrest, and hypoketotic hypoglycemia, while others present with unspecific symptoms such as failure to thrive, poor weight gain, and vomiting.…”