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Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease.
Rev Neurol (Paris). 2016 Mar; 172(3):231-41.RN

Abstract

INTRODUCTION

Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare, treatable, beta-oxidation disorder responsible for neuromuscular symptoms in adults. This case series describes the clinical and biochemical features of 13 French patients with late-onset MADD.

METHODS AND RESULTS

Thirteen ambulant patients (eight women, five men), with a median age at onset of 27 years, initially experienced exercise intolerance (n=9), isolated muscle weakness (n=1) and a multisystemic pattern with either central nervous system or hepatic dysfunction (n=3). During the worsening period, moderate rhabdomyolysis (n=5), a pseudomyasthenic pattern (n=5) and acute respiratory failure (n=1) have been observed. Weakness typically affected the proximal limbs and axial muscles, and there was sometimes facial asymmetry (n=3). Moderate respiratory insufficiency was noted in one case. Median baseline creatine kinase was 190IU/L. Lactacidemia was sometimes moderately increased at rest (3/10) and after exercise (1/3). The acylcarnitine profile was characteristic, with increases in all chain-length acylcarnitine species. Electromyography revealed a myogenic pattern, while muscle biopsy showed lipidosis, sometimes with COX-negative fibers (n=2). The mitochondrial respiratory chain was impaired in five cases, with coenzyme Q10 decreased in two cases. All patients harbored mutations in the ETFDH gene (four homozygous, seven compound heterozygous, two single heterozygous), with nine previously unidentified mutations. All patients were good responders to medical treatment, but exercise intolerance and/or muscular weakness persisted in 11 of them.

CONCLUSION

Late-onset forms of MADD may present as atypical beta-oxidation disorders. Acylcarnitine profiling and muscle biopsy remain the most decisive investigations for assessing the diagnosis. These tests should thus probably be performed more widely, particularly in unexplained cases of neuromuscular and multisystemic disorders.

Authors+Show Affiliations

AP-HP, Centre de Référence de Pathologie Neuromusculaire Paris-Est, Groupe Hospitalier Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France. Electronic address: anthony.behin@aphp.fr.Centre de Référence des Maladies Héréditaires du Métabolisme, Inserm U820, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 69500 Bron, France.AP-HP, Centre de Référence de Pathologie Neuromusculaire Paris-Est, Groupe Hospitalier Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France.Service de Neuropathologie, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Université Claude Bernard Lyon I, 69500 Bron, France.AP-HM, Centre de Référence des Maladies Neuromusculaires et de la SLA, CHU de La Timone, 13005 Marseille, France.AP-HP, Centre de Référence de Pathologie Neuromusculaire Paris-Ouest, CHU Henri-Mondor, Créteil, France.AP-HP, Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Robert-Debré, 75020 Paris, France.Centre de Référence lyonnais des Maladies Héréditaires du Métabolisme, Groupement Hospitalier Est, Hôpital Femme Mère-Enfant, CHU de Lyon, 69500 Bron, France.Centre de Référence Rhône-Alpes des Maladies Neuromusculaires, CHU de Grenoble, 38000 Grenoble, France.Service d'Anatomie et Cytologie pathologiques, CHU de Rouen, 76000 Rouen, France.Service de Médecine Interne, Hôpital Édouard-Herriot, 69437 Lyon cedex 03, France.Centre de Référence des Maladies Neuromusculaires, CHU de Nancy (Hôpitaux de Brabois), 54500 Vandœuvre-Lès-Nancy, France.AP-HM, Centre de Référence des Maladies Neuromusculaires et de la SLA, CHU de La Timone, 13005 Marseille, France.AP-HP, Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Robert-Debré, 75020 Paris, France.Centre de Compétences Pathologies Neuromusculaires Enfants, Néonatalogie et Réanimation Pédiatrique, CHU de Rouen, 76000 Rouen, France.AP-HP, Centre de Référence de Pathologie Neuromusculaire Paris-Est, Groupe Hospitalier Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France.Centre de Référence des Maladies Héréditaires du Métabolisme, Inserm U820, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 69500 Bron, France.AP-HP, Service de Biochimie, Hôpital de Bicêtre, 94270 Le Kremlin-Bicêtre, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27038534

Citation

Béhin, A, et al. "Multiple acyl-CoA Dehydrogenase Deficiency (MADD) as a Cause of Late-onset Treatable Metabolic Disease." Revue Neurologique, vol. 172, no. 3, 2016, pp. 231-41.
Béhin A, Acquaviva-Bourdain C, Souvannanorath S, et al. Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease. Rev Neurol (Paris). 2016;172(3):231-41.
Béhin, A., Acquaviva-Bourdain, C., Souvannanorath, S., Streichenberger, N., Attarian, S., Bassez, G., Brivet, M., Fouilhoux, A., Labarre-Villa, A., Laquerrière, A., Pérard, L., Kaminsky, P., Pouget, J., Rigal, O., Vanhulle, C., Eymard, B., Vianey-Saban, C., & Laforêt, P. (2016). Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease. Revue Neurologique, 172(3), 231-41. https://doi.org/10.1016/j.neurol.2015.11.008
Béhin A, et al. Multiple acyl-CoA Dehydrogenase Deficiency (MADD) as a Cause of Late-onset Treatable Metabolic Disease. Rev Neurol (Paris). 2016;172(3):231-41. PubMed PMID: 27038534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of late-onset treatable metabolic disease. AU - Béhin,A, AU - Acquaviva-Bourdain,C, AU - Souvannanorath,S, AU - Streichenberger,N, AU - Attarian,S, AU - Bassez,G, AU - Brivet,M, AU - Fouilhoux,A, AU - Labarre-Villa,A, AU - Laquerrière,A, AU - Pérard,L, AU - Kaminsky,P, AU - Pouget,J, AU - Rigal,O, AU - Vanhulle,C, AU - Eymard,B, AU - Vianey-Saban,C, AU - Laforêt,P, Y1 - 2016/03/30/ PY - 2015/09/09/received PY - 2015/11/11/revised PY - 2015/11/15/accepted PY - 2016/4/4/entrez PY - 2016/4/4/pubmed PY - 2017/1/24/medline KW - Acylcarnitine profile KW - ETFDH KW - Exercise intolerance KW - Multiple acyl-CoA dehydrogenase deficiency KW - Muscle lipidosis KW - Rhabdomyolysis SP - 231 EP - 41 JF - Revue neurologique JO - Rev. Neurol. (Paris) VL - 172 IS - 3 N2 - INTRODUCTION: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare, treatable, beta-oxidation disorder responsible for neuromuscular symptoms in adults. This case series describes the clinical and biochemical features of 13 French patients with late-onset MADD. METHODS AND RESULTS: Thirteen ambulant patients (eight women, five men), with a median age at onset of 27 years, initially experienced exercise intolerance (n=9), isolated muscle weakness (n=1) and a multisystemic pattern with either central nervous system or hepatic dysfunction (n=3). During the worsening period, moderate rhabdomyolysis (n=5), a pseudomyasthenic pattern (n=5) and acute respiratory failure (n=1) have been observed. Weakness typically affected the proximal limbs and axial muscles, and there was sometimes facial asymmetry (n=3). Moderate respiratory insufficiency was noted in one case. Median baseline creatine kinase was 190IU/L. Lactacidemia was sometimes moderately increased at rest (3/10) and after exercise (1/3). The acylcarnitine profile was characteristic, with increases in all chain-length acylcarnitine species. Electromyography revealed a myogenic pattern, while muscle biopsy showed lipidosis, sometimes with COX-negative fibers (n=2). The mitochondrial respiratory chain was impaired in five cases, with coenzyme Q10 decreased in two cases. All patients harbored mutations in the ETFDH gene (four homozygous, seven compound heterozygous, two single heterozygous), with nine previously unidentified mutations. All patients were good responders to medical treatment, but exercise intolerance and/or muscular weakness persisted in 11 of them. CONCLUSION: Late-onset forms of MADD may present as atypical beta-oxidation disorders. Acylcarnitine profiling and muscle biopsy remain the most decisive investigations for assessing the diagnosis. These tests should thus probably be performed more widely, particularly in unexplained cases of neuromuscular and multisystemic disorders. SN - 0035-3787 UR - https://www.unboundmedicine.com/medline/citation/27038534/Multiple_acyl_CoA_dehydrogenase_deficiency__MADD__as_a_cause_of_late_onset_treatable_metabolic_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0035-3787(16)00432-X DB - PRIME DP - Unbound Medicine ER -