Characterization of 31 Patients with Riboflavin-Responsive Multiple acyl-CoA Dehydrogenase Deficiency
Characterization of 31 Patients with Riboflavin-Responsive Multiple acyl-CoA Dehydrogenase Deficiency
Aims: To evaluate the clinical, pathological, and genetic features of patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD). Methods: Thirty-one patients with RR-MADD admitted to our hospital from January 2005 to November 2020 were enrolled, and their clinical data were collected. Pathological characteristics of the muscle tissue and possible pathogenic gene mutations were analyzed. Results: The most common clinical features in all patients were symmetrical proximal muscle weakness. Laboratory examination revealed elevated levels of creatine kinase, homocysteine, and uric acid, acylcarnitines, and organic acid. The muscle biopsy revealed typical pathological changes like lipid deposition. Genetic analysis identified ETFDH mutations in 29 patients, among which one had homozygotes, 19 had compound heterozygotes, 7 had heterozygous mutations, and 2 had heterozygous mutations of both ETFDH and ETFA. Two patients had no pathogenic gene mutations. All patients were treated with riboflavin, and their symptoms improved, which was consistent with the diagnosis of RR-MADD. Conclusion: The clinical manifestations and genetic test results of patients with RR-MADD are heterogeneous. Therefore, a comprehensive analysis of clinical, pathological, and genetic testing is essential for the early diagnosis of RR-MADD.
___
- Fu HX, Liu XY, Wang ZQ, et al. Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Neurol Sci. 2016; 37:1099-1105. [CrossRef]
- Olsen RK, Olpin SE, Andresen BS, et al. ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain. 2007;130:2045-2054. [CrossRef]
- Chokchaiwong S, Kuo YT, Hsu SP, et al. ETF-QO Mutants Uncoupled Fatty Acid β-Oxidation and Mitochondrial Bioenergetics Leading to Lipid Pathology. Cells. 2019;8:106. [CrossRef]
- Wen B, Dai T, Li W, et al. Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations. J Neurol Neurosurg Psychiatry. 2010;81:231-236. [CrossRef]
- Cwik VA. Disorders of lipid metabolism in skeletal muscle. Neurol Clin. 2000;18:167- 184. [CrossRef]
- Cui LY, Tang XF, Yuan J, Li BH, Du H. Clinical and neuroelectrophysiological study of lipid deposition myopathy with peripheral neuropathy. Chinese Journal of Neuroimmunology and Neurology. 1998;5:1557-1561. [CrossRef]
- Gempel K, Topaloglu H, Talim B, et al. The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. Brain. 2007;130: 2037-2044. [CrossRef]
- Xu J, Li D, Lv J, et al. ETFDH Mutations and Flavin Adenine Dinucleotide Homeostasis Disturbance Are Essential for Developing Riboflavin-Responsive Multiple Acyl-Coenzyme A Dehydrogenation Deficiency. Ann Neurol. 2018;84:659- 673. [CrossRef