Riboflavin-responsive multiple Acyl-CoA dehydrogenation deficiency in 13 cases, and a literature review in mainland Chinese patients

J Hum Genet. 2014 May;59(5):256-61. doi: 10.1038/jhg.2014.10. Epub 2014 Feb 13.

Abstract

Multiple Acyl-CoA dehydrogenation deficiency (MADD) is an autosomal recessive disorder of fatty acid oxidation and amino-acid metabolism. Most patients with late-onset MADD are well responsive to treatment with riboflavin, which is also termed as riboflavin-responsive MADD (RR-MADD). In this study, we summarized the clinical profiles and genetic features of 13 Chinese patients with RR-MADD and reanalyzed the existing data on RR-MADD patients in Mainland China. In a cohort comprising 13 patients, all were seen to present with severe muscular symptoms occasionally accompanied with mild involvements of extramuscular organs. A total of 18 mutations (13 reported and 5 novel) of the ETFDH gene were identified in this series of patients. Exon deletion/duplication was not found in all patients. ETF:QO expression from the muscle specimens was significantly decreased in all patients. At the time of this study the total number of RR-MADD cases had reached 148 in Mainland China since 2009. The muscle symptoms in Mainland China were similar to those in other regions. However, the common extramuscular symptoms were fatty liver and recurrent vomiting in mainland Chinese patients rather than encephalopathy found in Caucasian patients. A total of 68 mutations had been identified in 148 patients with RR-MADD. The c.250G>A had a high mutation frequency in Southern China, whereas c.770A>G and c.1227A>C were more geographically widespread hot spot mutations in Mainland China.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Asian Continental Ancestry Group
  • Biopsy
  • China
  • DNA Mutational Analysis
  • Electron-Transferring Flavoproteins / genetics
  • Exons
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Humans
  • Iron-Sulfur Proteins / genetics
  • Male
  • Middle Aged
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / diagnosis
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / drug therapy*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Mutation
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Riboflavin / therapeutic use*
  • Treatment Outcome

Substances

  • Electron-Transferring Flavoproteins
  • Iron-Sulfur Proteins
  • Oxidoreductases Acting on CH-NH Group Donors
  • electron-transferring-flavoprotein dehydrogenase
  • Riboflavin