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.

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