Multiple Acyl-Coenzyme a Dehydrogenase Deficiency Shows a Possible Founder Effect and Is the Most Frequent Cause of Lipid Storage Myopathy in Iran Publisher Pubmed



Nilipour Y¹ ; Fatehi F^{2, 3} ; Sanatinia S² ; Bradshaw A⁴ ; Duff J⁴ ; Lochmuller H^{5, 7, 8, 9} ; Horvath R⁶ ; Nafissi S²
Source: Journal of the Neurological Sciences Published:2020

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. © 2020 Elsevier B.V.