Nilipour Yalda, Fatehi Farzad, Sanatinia Saleheh, Bradshaw Anna, Duff Jennifer, Lochmüller Hanns, Horvath Rita, Nafissi Shahriar
Pediatric pathology research center, Research institute for children's health, AND Mofid Children Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Aix Marseille University, CNRS (UMR 7339), Centre de Resonance Magnétique Biologique et Medicale, Faculte de Medecine, 27 bd. J. Moulin, 13005 Marseille, France.
J Neurol Sci. 2020 Apr 15;411:116707. doi: 10.1016/j.jns.2020.116707. Epub 2020 Jan 23.
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.
多种酰基辅酶A脱氢酶缺乏症（MADD）是一种相对罕见的脂质代谢紊乱疾病。本研究旨在调查伊朗MADD的人口统计学、临床和遗传特征。
招募了29例确诊为脂质贮积性肌病的患者。所有患者均检测了ETFDH基因的突变，其中19例该基因存在双等位基因突变。
在19例确诊有突变的患者中，11例（57.9%）为女性，中位年龄为31岁。12例患者外显子10存在c.1130T>C（p.L377P）突变。2例患者有两个新的杂合子致病变体（外显子6的c.679C>T（p.P227S）和外显子7的c.814G>A（p.G272R）），2例患者外显子13存在c.1699G>A（p.E567K）突变。治疗前，中位肌肉力量为4.6（四分位间距：4-4.7），治疗后增至5（四分位间距：5-5）（Z=-3.71，p=.000）。治疗前肌酸激酶（CK）中位值为1848 U/l（四分位间距：1014-3473），治疗后降至188 U/l（四分位间距：117-397）（Z=-3.41，p=.001）。16例患者（84.2%）治疗后完全康复。与其他ETFDH突变患者（30岁；四分位间距：20-35）相比，纯合子c.1130T>C；p.（L377P）突变患者的疾病发病年龄更早（12岁；四分位间距：6-18）（p=.00）。
MADD有不同的临床表现。由于患者对治疗反应良好，早期诊断和治疗可预防该疾病的不可逆并发症。
