Multiple acyl-coenzyme A dehydrogenase deficiency shows a possible founder effect and is the most frequent cause of lipid storage myopathy in Iran

• Published in: Journal of the neurological sciences 2020-04, Vol.411, p.116707-116707, Article 116707
• Main Authors: Nilipour, Yalda, Fatehi, Farzad, Sanatinia, Saleheh, Bradshaw, Anna, Duff, Jennifer, Lochmüller, Hanns, Horvath, Rita, Nafissi, Shahriar
• Format: Article
• Language: English
• Subjects: Acyl-CoA Dehydrogenase; Adolescent; Adult; Child; Clinical; Electron-Transferring Flavoproteins - genetics; ETFDH gene; Female; Founder Effect; Genetics; Humans; Iran; Iron-Sulfur Proteins - genetics; Lipid Metabolism, Inborn Errors; Lipid storage myopathy; Male; Multiple Acyl Coenzyme A Dehydrogenase Deficiency - genetics; Multiple acyl-coenzyme A dehydrogenase deficiency; Muscular Dystrophies; Mutation - genetics; Oxidoreductases Acting on CH-NH Group Donors - genetics
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2020.116707

Multiple acyl-coenzyme A dehydrogenase deficiency disorder (MADD) is a relatively rare disorders of lipid metabolism. This study aimed to investigate the demographic, clinical, and genetic features of MADD in Iran. Twenty-nine patients with a definite diagnosis of lipid storage myopathy were recruited. All patients were tested for mutation in the ETFDH gene, and 19 had a biallelic mutation in this gene. Of 19 patients with definite mutations, 11 (57.9%) were female, and the median age was 31 years. Twelve patients had c.1130 T > C (p.L377P) mutation in exon 10. Two patients had two novel heterozygote pathogenic variants (c.679C > T (p.P227S) in exon 6 and c.814G > A (p.G272R) in exon 7) and two patients had c.1699G > A (p.E567K) in exon 13. Before treatment, the median muscle power was 4.6 (IQR: 4–4.7) that increased to 5 (IQR: 5–5) after treatment (Z = −3.71, p = .000). The median CK was 1848 U/l (IQR: 1014–3473) before treatment, which declined to 188 U/l (IQR: 117–397) after treatment (Z = −3.41, p = .001). Sixteen patients (84.2%) had full recovery after the treatment. The disease onset was earlier (12 years of age; IQR: 6–18) in patients with homozygous c.1130 T > C; p.(L377P) mutation compared to other ETFDH mutations (30 years of age; IQR: 20–35) (p = .00). MADD has different clinical presentations. As the patients respond favorably to treatment, early diagnosis and treatment may prevent the irreversible complications of the disease. [Display omitted] •MADDs are rare disorders of lipid metabolism due to mutation in the ETFDH gene.•We describe 19 Iranian patients with a biallelic mutation in the ETFDH.•We found two patients with two novel heterozygote pathogenic variants.•The patients had different clinical presentations.•Early diagnosis and treatment may prevent irreversible complications.