Late-onset multiple acyl-CoA dehydrogenase deficiency: an insidious presentation

BMJ Case Rep. 2023 May 22;16(5):e252668. doi: 10.1136/bcr-2022-252668.

Abstract

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism that results in impairment of mitochondrial β-oxidation of fatty acids. It is inherited in an autosomal recessive manner and impairs electron transfer in the electron transport chain. The clinical manifestations of MADD are highly variable and include exercise intolerance, myopathy, cardiomyopathy, encephalopathy, coma and death. Early-onset MADD is often associated with a high mortality with significant number of patients presenting with severe metabolic acidosis, non-ketotic hypoglycaemia and/or hyperammonaemic presentations. While late-onset MADD is suggested to have a lower mortality, the severe encephalopathic presentations may well be under-reported as a diagnosis of MADD may not be considered.MADD is treatable with riboflavin and appropriate nutrition with a focus on prevention and early management of metabolic decompensation. The neonatal phenotype differs significantly from late-onset MADD, where diagnosis may be delayed due to heterogeneity in clinical features, atypical presentation and confounding comorbidities, together with lower awareness among physicians.This report describes a woman in her 30s who presented with acute-onset ataxia, confusion and hyperammonaemic encephalopathy requiring intubation. Subsequent biochemical investigation revealed a diagnosis of MADD. At present, there are no national guidelines in Australia for the management of MADD. This case highlights the investigation and treatment of late-onset MADD.

Keywords: endocrinology; lipid disorders; metabolic disorders.

Publication types

  • Case Reports

MeSH terms

  • Acyl-CoA Dehydrogenase / genetics
  • Australia
  • Electron-Transferring Flavoproteins / genetics
  • Female
  • Humans
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency* / complications
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency* / diagnosis
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency* / genetics
  • Mutation
  • Riboflavin / therapeutic use

Substances

  • Electron-Transferring Flavoproteins
  • Riboflavin
  • Acyl-CoA Dehydrogenase