Late‐Onset Multiple Acyl‐CoA Dehydrogenase Deficiency (MADD): A Case Report With a Complex Biochemical Profile
Romain Penicaud,
Jean‐Baptiste Ferron,
Xavier Valette,
Pierrick Bauduin,
Maxime Faisant,
Manuel Schiff,
Alexandre Nguyen,
Fanny Fontaine,
Stéphane Allouche
Affiliations
Romain Penicaud
Department of Clinical Biochemistry Caen University Hospital Caen France
Jean‐Baptiste Ferron
Department of Internal Medicine Caen University Hospital Caen France
Xavier Valette
Department of Critical Care Medicine Caen University Hospital Caen France
Pierrick Bauduin
Department of Critical Care Medicine Caen University Hospital Caen France
Maxime Faisant
Department of Pathobiology Caen University Hospital Caen France
Manuel Schiff
Reference Center for Inborn Errors of Metabolism and Reference Center for Mitochondrial Disorders, Department of Pediatrics, Necker‐Enfants‐Malades Hospital, Assistance Publique‐Hôpitaux de Paris University of Paris‐Cité Paris France
Alexandre Nguyen
Department of Internal Medicine Falaise Hospital Falaise France
Fanny Fontaine
Department of Clinical Biochemistry Caen University Hospital Caen France
Stéphane Allouche
Department of Clinical Biochemistry Caen University Hospital Caen France
ABSTRACT Three clinical entities of multiple acyl‐CoA dehydrogenase deficiency (MADD, OMIM#231680) can be differentiated: two severe neonatal forms and one later‐onset form that can manifest in adulthood. The latter typically presents with muscle‐related symptoms, such as exercise intolerance and muscle weakness, with an increase in all chain‐length acylcarnitine species on the acylcarnitine profile. Here, we report the case of a 33‐year‐old woman who experienced severe psychiatric issues complicated by an eating disorder resulting in a significant malnutrition a few months before presenting with a profound muscle weakness, fatigue, intermittent ptosis, and a major rhabdomyolysis (creatine kinase (CK) > 15 000 IU/L). Biochemical blood tests, including acylcarnitine profile, urinary organic acid analysis, and in vitro beta‐oxidation, were not suggestive of a metabolic disease. Given the absence of an etiology and the worsening health condition of the patient, whole exome sequencing (WES) was performed and revealed two pathogenic variants in the electron transfer flavoprotein dehydrogenase (ETFDH) gene, whose association has not been reported before. Unlike other beta oxidation deficiencies, which have a typical biochemical signature, the diagnosis of MADD was made by genetic analyses, which allowed the introduction of vitamin B2 supplementation and the rapid improvement of symptoms.
