Novel ETFDH mutations in four cases of riboflavin responsive multiple acyl-CoA dehydrogenase deficiency

• Published in: Molecular genetics and metabolism reports Vol. 16; pp. 15 - 19
• Main Authors: Fan, Xin, Xie, Bobo, Zou, Jun, Luo, Jingsi, Qin, Zailong, D'Gama, Alissa M., Shi, Jiahai, Yi, Shang, Yang, Qi, Wang, Jin, Luo, Shiyu, Chen, Shaoke, Agrawal, Pankaj B., Li, Qifei, Shen, Yiping
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2018; Elsevier
• Subjects: ETF-QO; ETFDH; Glutaric aciduria II; Multiple acyl-CoA dehydrogenase deficiency; Research Paper; Riboflavin; AST; WES; ETFDH; Riboflavin; CK; ETF-QO; RR-MADD; LDH; ETF; MADD; Multiple acyl-CoA dehydrogenase deficiency; Glutaric aciduria II; GAII; MADD, multiple acyl-CoA dehydrogenase deficiency; LDH, lactate dehydrogenase; CK, creatine kinase; GAII, glutaric aciduria II; WES, whole exome sequencing; RR-MADD, riboflavin-responsive MADD; ETF-QO, ETF-ubiquinone oxidoreductase; ETF, electron transfer flavoprotein; AST, aspartate aminotransferase
• ISSN: 2214-4269; 2214-4269
• DOI: 10.1016/j.ymgmr.2018.05.007

Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid, and choline metabolism caused by mutations in EFTA, EFTB, or ETFDH. Many MADD patients are responsive to treatment with riboflavin, termed riboflavin-responsive MADD (RR-MADD). Here, we report three novel mutations and one previously reported mutation in ETFDH in four RR-MADD patients who presented at various ages, and characterize the corresponding changes in ETF-QO protein structure. Clinicians should consider MADD in the differential diagnosis when patients present with muscle weakness and biochemical abnormalities. Gene testing plays a critical role in confirming the diagnosis of MADD, and may not only prevent patients from invasive testing, but also allow timely initiation of riboflavin treatment. The novel variants in ETFDH and the corresponding clinical features reported here enrich the allelic heterogeneity of RR-MADD and provide insight into genotype-phenotype relationships.