Characterization of 31 Patients with Riboflavin-Responsive Multiple acyl-CoA Dehydrogenase Deficiency

Balkan Med J. 2022 Jul 22;39(4):290-296. doi: 10.4274/balkanmedj.galenos.2022.2022-1-127. Epub 2022 Jun 23.

Abstract

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.

MeSH terms

  • Electron-Transferring Flavoproteins / genetics
  • Humans
  • Iron-Sulfur Proteins* / genetics
  • Iron-Sulfur Proteins* / therapeutic use
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency* / diagnosis
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency* / drug therapy
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency* / genetics
  • Oxidoreductases Acting on CH-NH Group Donors* / genetics
  • Riboflavin / pharmacology
  • Riboflavin / therapeutic use

Substances

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