High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late‐onset lipid storage myopathy

Abstract

Lipid storage myopathies (LSMs) are characterized pathologically by the accumulation of lipid droplets in muscle fibers due to impaired cellular lipid metabolism. The purpose of this study was to determine etiologies and genetic mutations associated with LSMs in ethnic Han Taiwanese. The usefulness of the blood acylcarnitine (AC) profile for diagnosing LSMs in adult patients was also investigated. Nine patients were diagnosed with late-onset LSMs following a review of muscle biopsies and medical records and were recruited retrospectively. Genetic studies were performed to detect mutations in the SLC22A5 for primary carnitine deficiency, PNPLA2 for neutral lipid storage disease with myopathy, ABHD5 for neutral lipid storage disease with ichthyosis, ETFDH for multiple acyl-CoA dehydrogenation deficiency (MADD), and CPT2 for carnitine palmitoyltransferase II deficiency. Blood AC levels were measured by tandem mass spectrometry. The mutation c.250G>A in ETFDH was detected in seven (78%) patients, six of whom were homozygous for the variant. Patients with ETFDH mutations had elevated blood levels of ACs ranging from C8 to C16 species, a pattern consistent with MADD. ETFDH c.250G>A mutation is common in Taiwanese patients with late-onset LSMs. The blood AC profile is a sensitive biochemical marker for diagnosing MADD arising from ETFDH mutations in adults.

A case of late-onset riboflavin responsive multiple acyl-CoA dehydrogenase deficiency (MADD) with a novel mutation in ETFDH gene

“…The phenotype is speculated to correlate with the genotype. Mutations in ETFA and ETFB tend to be early-onset forms, whereas mutations in ETFDH are associated with late-onset MADD, especially the RR-MADD [3,4,[7][8][9]. By now, more than 80 mutations have been reported all over the world, but the same mutant site is rarely found in different (Fig.…”

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

“…Using an improved interpretive tool (Marquardt et al 2012), we retrospectively detected one patient and confirmed the increased sensitivity of this tool. This is especially important because the incidence of the riboflavin-responsive form of MAD deficiency is high in Taiwan (Liang et al 2009;Lan et al 2010) and Southern China (Wang et al 2011) owing to a high incidence of the p.A84T mutation in the ETFDH gene (a carrier rate of 1 in 74), and the treatment with carnitine and riboflavin is easy and effective.…”

Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders

“…This defect thy, displaying characteristic fatty infi ltration of the heart, kidneys, and liver. The third presentation is late onset, which is a milder form with variable symptoms, including lipid storage myopathy ( 215 ).…”