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Figure 1: Distal atrophy and foot drop (Bilateral but more prominent on the right) (A), pes cavus and claw toes on the left foot (B).

Dermographism was found positive in the patient who described more than expected injuries after hard contact with his skin (Figure 2).

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Figure 2: Dermatographism and skin lesion due to sensitivity to previous trauma.

In nerve conduction studies, findings consistent with distal prominent motor axonal neuropathy were observed (Table 1). The patient's cognitive functions and brain MR imaging are within normal limits.

Table 1. Nerve conduction studies at the first admission of the patient.

Genetic Evaluation
DNA extraction was performed according to instructions (Maxwell RSC Blood DNA kit, Promega, USA). The concentration of DNA samples was determined using Qubit 3.0 (Thermo Fisher Scientific). The libraries for sequencing were constructed following the instructions of Twist Human Core Exome Kit protocol (Twist Bioscience, USA). Next-gene sequencing was performed on a Novaseq system (Illumina, USA). Sequence data analysis using Sophia DDM (Switzerland). The analysis revealed a homozygous variation (c.755G>T p.(Gly252Val)) in the SORD gene. On the other hand, silico prediction data bases, such as MetaRNN, BayesDel, PROVEAN, CADD, SIFT indicated that the variation was classified as 'pathogenic.' In addition, this variant has not been observed as homozygous in the healthy population according to Genome Aggregation Database (gnomAD). According to the American College of Medical Genetics (ACMG) 2015 criteria (Richards S, Aziz N, Bale S, et al. Standards and Guidelines for the Interpretation of Sequence Variants: a Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May; 17 (5): 405-24.), the variant was clas-sified as class 3 clinical significance. Our opinion that given the similarity between the patient's clinical presentation and the expected findings of the "sorbitol dehydrogenase deficiency" phenotype caused by homozygous pathogenic variant features, the patient in the similar variant has the expected findings of the "sorbitol dehydrogenase deficiency with peripheral neuropathy".

These 4 cases were reported as dHMN⁸. In a study conducted in the Czech Republic, a homozygous c.757del(Ala253Glnfs*27) mutation was found in nine of 18 cases from 16 different families, and in the other 9 cases the compound heterozygous second allele was 6×c.458C>A p.(Ala153Asp), 1×c.218C>. T p.(Ser73Leu), 1×c.503G>A p.(Gly168Asp), and 1×c.553G>A p.(Gly185Arg) were seen. Two of these 18 cases were reported as dHMN, 14 cases as CMT2 and two cases as CMT intermediate type¹⁰. SORD is one of the two enzymes that causes intracellular oxidative stress caused by hyperglycemia by converting sorbitol to fructose via polyol pathway using the NAD cofactor. The other enzyme is aldose reductase (AR). AR, which uses the NADPH cofactor, it converts glucose to sorbitol and participates in the polyol pathway¹¹. SORD defect causes synaptic degeneration and progressive motor impairment⁹. It has been observed that aldose reductase inhibitors can be effective in SORD defective cell models and it has been stated that they increase the climbing ability in these patients^12,13. Just like aldose reductase inhibitors, many hopeful genetic studies are in progress in clinical trials^12,14.

DISCLOSURE
Conflict of interests: No conflict of interest was declared by the authors.

Financial support: No financial support was received for the study.

Consent Form: Informed voluntary consent form was taken from the patient.

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