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 longchain 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. Communicated by: Manuel SchiffPeter van Vliet and Annelies E. Berden contributed equally to this work. Electronic supplementary material:The online version of this chapter

Charcot–Marie–Tooth Disease With Episodic Rhabdomyolysis Due to Two Novel Mutations in the β Subunit of Mitochondrial Trifunctional Protein and Effective Response to Modified Diet Therapy

“…However, in the literature, late-onset neuromuscular MTPD with outcome of dietary treatment only accounted for a small portion of this subtype. A possible reason is that adult patients showed poor compliance to the recommended dietary plan ( 5 , 19 ). Our patient reacted well because we tailored a diet regimen in accordance with the above principles by combining formula nutrients with selected foods, which was more readily accepted and adhered to by the patient.…”

Mitochondrial trifunctional protein deficiency as a polyneuropathy etiology in childhood

“…et al 12 reported peripheral polyneuropathy, rhabdomyolysis, and infantileonset hypoparathyroidism in two siblings with HADHB gene mutations. Recently, van Vliet et al 13 reported a 20-year-old woman who had axonal motor-sensory polyneuropathy of unknown origin since childhood. She presented with progressive dyspnea, and increased muscle weakness which had been preceded by an infectious disease.…”

Case report: Mitochondrial trifunctional protein deficiency caused by HADHB gene mutation (c.1175C>T) characterized by higher brain dysfunction followed by neuropathy, presented gadolinium enhancement on brain imaging in an adult patient

“…In some late-onset cases, the symptoms of peripheral neuropathy are similar to those of Charcot–Marie–Tooth disease (CMT) ( 4 , 5 ). Additionally, some cases are complicated by hypoparathyroidism ( 6 , 7 ).…”