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Peripheral Neuropathy, Episodic Rhabdomyolysis, and Hypoparathyroidism in a Patient with Mitochondrial Trifunctional Protein Deficiency

  • Peter van Vliet
  • Annelies E. Berden
  • Mojca K. M. van Schie
  • Jaap A. Bakker
  • Christian Heringhaus
  • Irenaeus F. M. de Coo
  • Mirjam Langeveld
  • Marielle A. Schroijen
  • M. Sesmu Arbous
Research Report
Part of the JIMD Reports book series (JIMD, volume 38)

Abstract

A combination of unexplained peripheral neuropathy, hypoparathyroidism, and the inability to cope with metabolic stress could point to a rare inborn error of metabolism, such as mitochondrial trifunctional protein (MTP) deficiency.

Here, we describe a 20-year-old woman who was known since childhood with axonal motor sensory polyneuropathy of unknown origin. She presented with progressive dyspnoea, and increased muscle weakness, preceded by 6 days of fever, vomiting, and diarrhoea. Laboratory testing showed rhabdomyolysis, and hypocalcaemia with low parathyroid levels. The patient was intubated because of respiratory insufficiency and a viral and bacterial pneumonia was diagnosed. She was discharged after 16 days of admission. Metabolic screening, performed at the time of rhabdomyolysis, showed increased concentrations of long-chain 3-hydroxyacyl carnitine species, together with elevated urinary excretion of 3-hydroxy dicarboxylic acids. Decreased activity of long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-ketoacyl-CoA thiolase in peripheral lymphocytes and fibroblasts confirmed a MTP deficiency. Sequence analysis of the HADHB gene showed two heterozygous variants: c.209+1G>C (splicing defect) and c.980T>C (p.Leu327Leu). When the acylcarnitine profile was repeated after the episode of rhabdomyolysis had resolved it showed no abnormalities.

Our case illustrates a cluster of peripheral neuropathy, episodic rhabdomyolysis, and hypoparathyroidism in a patient with MTP deficiency caused by mutations in the HADHB gene. It stresses the importance of performing metabolic screening when patients are most symptomatic, as normal results can be found at times when no metabolic stress is present. Screening is relatively easy and timely diagnosis has important implications for treatment.

Keywords

Hypoparathyroidism MTP deficiency Peripheral neuropathy Rhabdomyolysis 

Supplementary material

464154_1_En_37_MOESM1_ESM.docx (14 kb)
Supplementary Table 1 Nerve conduction studies (DOCX 15 kb)

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Peter van Vliet
    • 1
  • Annelies E. Berden
    • 2
  • Mojca K. M. van Schie
    • 3
  • Jaap A. Bakker
    • 4
  • Christian Heringhaus
    • 5
  • Irenaeus F. M. de Coo
    • 6
  • Mirjam Langeveld
    • 7
  • Marielle A. Schroijen
    • 2
  • M. Sesmu Arbous
    • 1
  1. 1.Department of Intensive Care MedicineLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of Internal MedicineLeiden University Medical CenterLeidenThe Netherlands
  3. 3.Department of NeurologyLeiden University Medical CenterLeidenThe Netherlands
  4. 4.Department of Clinical ChemistryLeiden University Medical CenterLeidenThe Netherlands
  5. 5.Emergency DepartmentLeiden University Medical CenterLeidenThe Netherlands
  6. 6.Department of NeurologyErasmus University Medical CenterRotterdamThe Netherlands
  7. 7.Department of Endocrinology and MetabolismAcademic Medical Centre, University of AmsterdamAmsterdamThe Netherlands

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