Novel mutations in the HADHB gene causing a mild phenotype of mitochondrial trifunctional protein (MTP) deficiency

Kristin Ørstavik; Kjell Arne Arntzen; Per Mathisen; Paul Hoff Backe; Trine Tangeraas; Magnhild Rasmussen; Erle Kristensen; Marijke Van Ghelue; Christoffer Jonsrud; Yngve Thomas Bliksrud

doi:10.1002/jmd2.12276

Novel mutations in the HADHB gene causing a mild phenotype of mitochondrial trifunctional protein (MTP) deficiency

JIMD Rep. 2022 Mar 1;63(3):193-198. doi: 10.1002/jmd2.12276. eCollection 2022 May.

Authors

Affiliations

¹ Department of Neurology, Section for Rare Neuromuscular disorders and EMAN Oslo University Hospital, Rikshospitalet Oslo Norway.
² National Neuromuscular Centre Norway and Department of Neurology University Hospital of North Norway Tromsø Norway.
³ Department of Cardiology Oslo University Hospital, Rikshospitalet Oslo Norway.
⁴ Department of Microbiology Oslo University Hospital, Rikshospitalet and University of Oslo Oslo Norway.
⁵ Department of Medical Biochemistry Institute for Clinical Medicine, University of Oslo Oslo Norway.
⁶ Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine Oslo University Hospital Oslo Norway.
⁷ Department of Clinical Neurosciences for Children Oslo University Hospital, Rikshospitalet Oslo Norway.
⁸ Department of Medical Biochemistry Oslo University Hospital, Rikshospitalet Oslo Norway.
⁹ Department of Medical Genetics, Division of Child and Adolescent Health University Hospital of North Norway Tromsø Norway.

Abstract

Mitochondrial trifunctional protein (MTP) deficiency is an ultrarare hereditary recessive disorder causing a broad spectrum of phenotypes with lethal infantile cardiomyopathy at the most severe end. Attenuated forms with polyneuropathy have been reported combined with myoglobinuria or rhabdomyolysis as key features. We here report three young adults (two siblings) in which three variants in the HADHB-gene were identified. All three cases had a similar mild phenotype with axonal neuropathy and frequent intermittent weakness episodes but without myoglobinuria. Special dietary precautions were recommended to minimize complications especially during infections and other catabolic states. MTP deficiency is therefore an important differential diagnosis in patients with milder fluctuating neuromuscular symptoms.

Take‐home message: Axonal neuropathy and recurrent muscular weakness without concomitant rhabdomyolysis may be due to MTP deficiency.

Keywords: HADHB; MTP; mutation; neuropathy; weakness.

Publication types

Case Reports