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

J Neurol Sci. 2020 Apr 15;411:116707. doi: 10.1016/j.jns.2020.116707. Epub 2020 Jan 23.

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Discussion: MADD has different clinical presentations. As the patients respond favorably to treatment, early diagnosis and treatment may prevent the irreversible complications of the disease.

Keywords: Clinical; ETFDH gene; Genetics; Iran; Lipid storage myopathy; Multiple acyl-coenzyme A dehydrogenase deficiency.