Yalda Nilipour1, Farzad Fatehi2, Saleheh Sanatinia3, Anna Bradshaw4, Jennifer Duff4, Hanns Lochmüller5, Rita Horvath6, Shahriar Nafissi7. 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. 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. 3. Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 4. Wellcome Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. 5. Department of Neuropediatrics and Muscle Disorders, Medical Center - the University of Freiburg, Faculty of Medicine, Freiburg, Germany; Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada; Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada. 6. Department of Clinical Neurosciences, University of Cambridge School of Clinical Medicine, Cambridge, UK. Electronic address: Rh732@medschl.cam.ac.uk. 7. Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: nafisi@tums.ac.ir.
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.
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.
Authors: Maria Anna Siano; Claudia Mandato; Lucia Nazzaro; Gennaro Iannicelli; Gian Paolo Ciccarelli; Ferdinando Barretta; Cristina Mazzaccara; Margherita Ruoppolo; Giulia Frisso; Carlo Baldi; Salvatore Tartaglione; Francesco Di Salle; Daniela Melis; Pietro Vajro Journal: Front Pediatr Date: 2021-05-10 Impact factor: 3.418