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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 F2, 3 ; Sanatinia S2 ; Bradshaw A4 ; Duff J4 ; Lochmuller H5, 7, 8, 9 ; Horvath R6 ; Nafissi S2
Authors
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Authors Affiliations
  1. 1. 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
  2. 2. Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Aix Marseille University, CNRS (UMR 7339), Centre de Resonance Magnetique Biologique et Medicale, Faculte de Medecine, 27 bd. J. Moulin, Marseille, 13005, France
  4. 4. Wellcome Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
  5. 5. Department of Neuropediatrics and Muscle Disorders, Medical Center – the University of Freiburg, Faculty of Medicine, Freiburg, Germany
  6. 6. Department of Clinical Neurosciences, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
  7. 7. Centro Nacional de Analisis Genomico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
  8. 8. Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada
  9. 9. Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada

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.