Sensory neuronopathy as a major clinical feature of mitochondrial trifunctional protein deficiency in adults

Y Nadjar; S Souvannanorath; T Maisonobe; M Brisset; P De Lonlay; M Schiff; K Viala; A Boutron; G Nicolas; P Laforêt

doi:10.1016/j.neurol.2019.11.011

Sensory neuronopathy as a major clinical feature of mitochondrial trifunctional protein deficiency in adults

Rev Neurol (Paris). 2020 May;176(5):380-386. doi: 10.1016/j.neurol.2019.11.011. Epub 2020 Apr 3.

Authors

Y Nadjar¹, S Souvannanorath², T Maisonobe³, M Brisset⁴, P De Lonlay⁵, M Schiff⁶, K Viala⁷, A Boutron⁸, G Nicolas⁹, P Laforêt¹⁰

Affiliations

¹ Département de neurologie, centre de référence des maladies lysosomales, UF neuro-génétique et métabolisme, groupe hospitalier Pitié-Salpêtrière, Assistance publique-Hôpitaux de Paris, Paris, France. Electronic address: [email protected].
² Centre de référence des maladies neuromusculaires, hôpital Henri-Mondor, Assistance publique-Hôpitaux de Pars, Créteil, France. Electronic address: [email protected].
³ Département de neurophysiologie clinique, groupe hospitalier Pitié-Salpêtrière, Assistance publique-Hôpitaux de Paris, Paris, France. Electronic address: [email protected].
⁴ Département de neurologie, hôpital Raymond-Poincaré, Garches, France; Inserm U1179 Versailles Saint-Quentin-en-Yvelines university, 78180 Montigny-le-Bretonneux, France. Electronic address: [email protected].
⁵ Reference center for inborn errors of metabolism, Necker-Enfants-Malades university hospital, AP-HP, Paris Descartes university, INSERM UMR_S1151, 75015 Paris, France. Electronic address: [email protected].
⁶ Reference center for inborn errors of metabolism, Robert-Debré university hospital, AP-HP, Paris Diderot university, INSERM U1141, 75019 Paris, France. Electronic address: [email protected].
⁷ Département de neurophysiologie clinique, groupe hospitalier Pitié-Salpêtrière, Assistance publique-Hôpitaux de Paris, Paris, France. Electronic address: [email protected].
⁸ Service de biochimie, hôpital de Bicêtre, CHU Paris - GH Paris-Sud, Paris, France. Electronic address: [email protected].
⁹ Département de neurologie, hôpital Raymond-Poincaré, Garches, France; Inserm U1179 Versailles Saint-Quentin-en-Yvelines university, 78180 Montigny-le-Bretonneux, France. Electronic address: [email protected].
¹⁰ Département de neurologie, hôpital Raymond-Poincaré, Garches, France; Inserm U1179 Versailles Saint-Quentin-en-Yvelines university, 78180 Montigny-le-Bretonneux, France. Electronic address: [email protected].

PMID: 32253025
DOI: 10.1016/j.neurol.2019.11.011

Abstract

Introduction: Mitochondrial trifunctional protein deficiency (MTPD) is a long-chain fatty acid oxidation disorder characterized by co-existence of rhabdomyolysis episodes and peripheral neuropathy. Two phenotypes are described: generalized mitochondrial trifunctional protein deficiency (gMTPD) and isolated long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency (iLCHADD) that is always associated with the c.1528G>C mutation. Peripheral neuropathy of MTPD is commonly described in children as axonal, length-dependent and sensorimotor.

Objectives: To report clinical and electrophysiological features of four independent adult MTPD patients with peripheral neuropathy.

Results: Onset of the disease was characterized in all patients by rhabdomyolysis episodes occurring during childhood preceded by severe hypoglycemic episodes in three patients. Peripheral nerve involvement manifesting as sensory ataxia appeared later, during adolescence or adulthood. In all cases, electroneuromyogram showed no length-dependent sensory potentials decrease characteristic of sensory neuronopathy ("ganglionopathy"). All patients harbored at least one c.1528G>C mutation.

Discussion: We describe MTPD as a newly hereditary etiology of sensory neuronopathy in adults, specifically in patients with c.1528G>C mutation. MTPD should be screened for by performing plasma acylcarnitines in patients with chronic sensory neuronopathy and additional suggestive features such as exercise intolerance or retinopathy.

Keywords: Ganglionopathy; LCHAD deficiency; MTP deficiency; Rhabdomyolysis; Sensory neuronopathy.

Publication types

Case Reports

MeSH terms

Adult
Age Factors
Cardiomyopathies / complications*
Cardiomyopathies / diagnosis*
Cardiomyopathies / pathology
Female
Humans
Lipid Metabolism, Inborn Errors / complications*
Lipid Metabolism, Inborn Errors / diagnosis*
Lipid Metabolism, Inborn Errors / pathology
Male
Middle Aged
Mitochondrial Myopathies / complications*
Mitochondrial Myopathies / diagnosis*
Mitochondrial Myopathies / pathology
Mitochondrial Trifunctional Protein / deficiency*
Nervous System Diseases / complications*
Nervous System Diseases / diagnosis*
Nervous System Diseases / pathology
Peripheral Nervous System Diseases / diagnosis*
Peripheral Nervous System Diseases / etiology*
Peripheral Nervous System Diseases / pathology
Phenotype
Rhabdomyolysis / complications*
Rhabdomyolysis / diagnosis*
Rhabdomyolysis / pathology
Young Adult

Substances

Mitochondrial Trifunctional Protein

Supplementary concepts

Trifunctional Protein Deficiency With Myopathy And Neuropathy