Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep;44(9):3037-3043.
doi: 10.1007/s10072-023-06790-0. Epub 2023 Apr 12.

FDXR-associated disease: a challenging differential diagnosis with inflammatory peripheral neuropathy

Silvia Masnada  1 , Roberto Previtali  2   3 , Paola Erba  4 , Elena Beretta  5 , Anna Camporesi  6 , Luisa Chiapparini  7 , Chiara Doneda  8 , Maria Iascone  9 , Marco U A Sartorio  4 , Luigina Spaccini  10 , Pierangelo Veggiotti  2   3 , Maurizio Osio  11 , Davide Tonduti  2   3 , Isabella Moroni  12
Affiliations

FDXR-associated disease: a challenging differential diagnosis with inflammatory peripheral neuropathy

Silvia Masnada et al. Neurol Sci. 2023 Sep.

Abstract

Background and aims: Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common presentation includes optic and/or auditory neuropathy, variably associated to developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures. The review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.72%) and ataxia (43.18%). To date, 44 patients with FDXR mutations have been reported. We describe here on two new patients, siblings, who presented with a quite different phenotype compared to previously described patients.

Methods: Clinical, neurophysiological, and genetic features of two siblings and a systematic literature review focused on the clinical spectrum of the disease are described.

Results: Both patients presented with an acute-sub-acute onset of peripheral neuropathy and only in later stages of the disease developed the typical features of FDXR-associated disease.

Interpretation: The peculiar clinical presentation at onset and the evolution of the disease in our patients and in some cases revised from the literature shed lights on a new possible phenotype of FDXR-associated disease: a peripheral neuropathy which can mimic an acute inflammatory disease.

Keywords: FDXR; Peripheral neuropathy; Phenotype.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
MR examination performed at the onset of symptoms and at follow-up: A axial T2-weighted image at the level of craniocervical junction demonstrates subtle T2 signal hyperintensities in the posterior columns of spinal cord (arrows). B Axial post-contrast T1-weighted image at the level of cauda equina shows contrast enhancement of posterior roots (arrows). C–D Follow-up MR examination performed 1 year later (same sections and technique, respectively, of A and B). C Resolution of signal abnormalities in posterior columns. D No more evidence of posterior roots contrast enhancement
See this image and copyright information in PMC

References

    1. Paul A, Drecourt A, Petit F, Deguine DD, et al. FDXR mutations cause sensorial neuropathies and expand the spectrum of mitochondrial Fe-S-synthesis diseases. Am J Hum Genet. 2017;101(4):630–637. doi: 10.1016/j.ajhg.2017.09.007. - DOI - PMC - PubMed
    1. Slone J, Peng Y, Chamberlin A, Harris B, et al. Biallelic mutations in FDXR cause neurodegeneration associated with inflammation. J Hum Genet. 2018;63(12):1211–1222. doi: 10.1038/s10038-018-0515-y. - DOI - PMC - PubMed
    1. Slone JD, Yang L, Peng Y, Queme LF, et al. Integrated analysis of the molecular pathogenesis of FDXR-associated disease. Cell Death Dis. 2020;11(6):423. doi: 10.1038/s41419-020-2637-3. - DOI - PMC - PubMed
    1. Stenton SL, Piekutowska-Abramczuk D, Kulterer L, Kopajtich R et al (2021) Expanding the clinical and genetic spectrum of FDXR deficiency by functional validation of variants of uncertain significance. Hum Mutat 42(3):310–319. 10.1002/humu.24160 - PubMed
    1. Pezzani L, Marchetti D, Cereda A, Caffi LG et al (2018) Atypical presentation of pediatric BRAF RASopathy with acute encephalopathy. Am J Med Genet A 176(12):2867–2871. 10.1002/ajmg.a.40635 - PubMed

Publication types

Substances