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. 2023 Jul;30(7):2001-2011.
doi: 10.1111/ene.15793. Epub 2023 Apr 4.

SORD-related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages

Nicolas Pons  1   2 , Gorka Fernández-Eulate  3 , Antoine Pegat  4   5   6 , Marie Théaudin  7 , Régis Guieu  2 , Paolo Ripellino  8 , Manon Devedjian  1 , Patrick Mace  2 , Marion Masingue  3 , Sarah Léonard-Louis  3 , Philipe Petiot  4 , Pauline Roche  4 , Emilien Bernard  4   5   6 , Françoise Bouhour  4   6 , Jean-Marc Good  9 , Annie Verschueren  10 , Aude-Marie Grapperon  10 , Emmanuelle Salort  10 , Anaïs Grosset  11 , Jean-Baptiste Chanson  12 , Aleksandra Nadaj-Pakleza  12 , Anne-Laure Bédat-Millet  13 , Ariane Choumert  14 , Anne Barnier  15 , Ghassen Hamdi  15 , Gaëtan Lesca  16   17 , Fabienne Prieur  18 , Arnaud Bruneel  15 , Philippe Latour  6   19 , Tanya Stojkovic  3 , Shahram Attarian  10 , Nathalie Bonello-Palot  1   20
Affiliations

SORD-related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages

Nicolas Pons et al. Eur J Neurol. 2023 Jul.

Abstract

Background and purpose: Biallelic variants in SORD have been reported as one of the main recessive causes for hereditary peripheral neuropathies such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathy (dHMN) resulting in lower limb (LL) weakness and muscular atrophy. In this study, phenotype and genotype landscapes of SORD-related peripheral neuropathies were described in a French and Swiss cohort. Serum sorbitol dosages were used to classify SORD variants.

Methods: Patients followed at neuromuscular reference centres in France and Switzerland were ascertained. Sanger sequencing and next generation sequencing were performed to sequence SORD, and mass spectrometry was used to measure patients' serum sorbitol.

Results: Thirty patients had SORD peripheral neuropathy associating LL weakness with muscular atrophy, foot deformities (87%), and sometimes proximal LL weakness (20%) or distal upper limb weakness (50%). Eighteen had dHMN, nine had CMT2, and three had intermediate CMT. Most of them had a mild or moderate disease severity. Sixteen carried a homozygous c.757delG (p.Ala253Glnfs*27) variant, and 11 carried compound heterozygous variants, among which four variants were not yet reported: c.403C > G, c.379G > A, c.68_100 + 1dup, and c.850dup. Two unrelated patients with different origins carried a homozygous c.458C > A variant, and one patient carried a new homozygous c.786 + 5G > A variant. Mean serum sorbitol levels were 17.01 mg/L ± 8.9 SD for patients carrying SORD variants.

Conclusions: This SORD-inherited peripheral neuropathy cohort of 30 patients showed homogeneous clinical presentation and systematically elevated sorbitol levels (22-fold) compared to controls, with both diagnostic and potential therapeutic implications.

Keywords: SORD; Charcot-Marie-Tooth; muscular atrophy; neuropathy; peripheral neuropathy.

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References

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