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

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.

Peter van Vliet and Annelies E. Berden contributed equally to this work.

Synopsis

Mitochondrial trifunctional protein deficiency can present as a cluster of peripheral neuropathy, hypoparathyroidism, and episodic exacerbations during metabolic stress, with the important notice that metabolic screening may be normal when performed when no metabolic stress is present.

Compliance with Ethics Guidelines

Author Contributions

All authors were involved in drafting the manuscript and revising it critically for important intellectual content and have agreed upon submission of the manuscript.

Competing Interest/Funding

Peter van Vliet, Annelies Berden, Mojca van Schie, Jaap Bakker, Christian Heringhaus, Irenaeus de Coo, Mirjam Langeveld, Marielle Schroijen, and Sesmu Arbous declare that they have no conflicts of interest. This case report was not supported by any funding source.

Ethics Approval/Consent

This case report did not need evaluation by a medical ethical committee. Informed consent to publish the case report was obtained from the patient.