TY - JOUR
T1 - Peripheral Neuropathy, Episodic Rhabdomyolysis, and Hypoparathyroidism in a Patient with Mitochondrial Trifunctional Protein Deficiency
AU - van Vliet, Peter
AU - Berden, Annelies E.
AU - van Schie, Mojca K. M.
AU - Bakker, Jaap A.
AU - Heringhaus, Christian
AU - de Coo, Irenaeus F. M.
AU - Langeveld, Mirjam
AU - Schroijen, Marielle A.
AU - Arbous, M. Sesmu
PY - 2018
Y1 - 2018
N2 - 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
AB - 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
U2 - https://doi.org/10.1007/8904_2017_37
DO - https://doi.org/10.1007/8904_2017_37
M3 - Article
C2 - 28685493
SN - 2192-8304
VL - 38
SP - 101
EP - 105
JO - JIMD reports
JF - JIMD reports
ER -