Clinical and biological features at diagnosis in mitochondrial fatty acid beta‐oxidation defects: a French pediatric study of 187 patients

Abstract

This study presents clinical features of a large cohort of patients with FAODs in a country without neonatal screening for FAODs. Our results highlight liver as the main organ involved at diagnosis regardless of age at diagnosis, classical phenotype (i.e., cardiac, hepatic, or muscular), or enzyme deficiency. Although steatosis may be observed in various inherited metabolic defects, it is a reliable indicator of FAOD and should prompt systematic screening when the diagnosis is suspected. The poor long-term prognoses reported are a strong argument for inclusion of FAODs in newborn screening programs.

Birth Prevalence of Fatty Acid β-Oxidation Disorders in Iberia

“…Treatment options include avoiding fasting, which is in some cases complemented with carnitine, riboflavin or CoQ10 supplementation (Spiekerkoetter et al 2010) and leads in most cases to favourable prognosis following diagnosis, being FAOD associated with high mortality/ morbidity rates for those diagnosed later in a symptomatic phase (Baruteau et al 2013). The effectiveness of available treatments for most of FAOD patients, the availability of high throughput adapted tests (acylcarnitine analysis on dried blood spots) and the advantages of an early intervention made this group of disorders main targets for Newborn Screening (NBS) programs worldwide (Lindner et al 2010;Bennett et al 2012;Baruteau et al 2013).…”

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

“…Before newborn screening for these disorders, FAO disorders were characterized by high morbidity and mortality (Wanders et al 1999) and required strict treatment measures. The mortality rate of FAO disorders was approximately 48% but could be higher in specific diseases such as VLCAD deficiency (60%) or CATC deficiency (92%) (Baruteau et al 2012). After the development of tandem mass spectrometry (MS/MS) analysis of acylcarnitines (Millington et al 1990), the number of disorders that could be detected by newborn screening greatly increased (Huang et al 2006), and most aminoacidopathies, FAO disorders, and organic acidurias became diagnosable.…”

“…The combined incidence of FAO disorders reaches 1:9,000 in some countries, and half of the detected patients are affected by MCAD deficiency (Zytkovicz et al 2001;Lindner et al 2010). Early institution of high-glucose infusion, a low-fat diet, and avoidance of fasting can prevent the occurrence of metabolic decompensation (Baruteau et al 2012). Therefore, MS/MS newborn screening (NBS) has been shown to improve the outcome of patients, and this screening is also cost effective (Pandor et al 2004).…”

Strategies for Correcting Very Long Chain Acyl-CoA Dehydrogenase Deficiency

“…Children with the most severe form of VLCAD deficiency present with cardiomyopathy and hepatic failure. This severe form is generally fatal in the 1st year of life (12)(13)(14)(15)(16)22). A milder phenotype presents during early childhood with hypoketotic hypoglycemia and hepatomegaly without cardiomyopathy.…”

“…A milder phenotype presents during early childhood with hypoketotic hypoglycemia and hepatomegaly without cardiomyopathy. The mildest phenotype is associated with later onset episodic myopathic form with intermittent rhabdomyolysis, muscle cramps, and/or pain and exercise intolerance (12)(13)(14)(15)(16)22).…”