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Abstract
Discussion Forum (0)
Sorbitol-Dehydrogenase (SORD) gene Mutation as a Curable Cause of Charcot-Marie-Tooth 2 (CMT-2) and Distal Hereditary Motor Neuronopathy (d-HMN)
Poster No: 1367
Presenter: Gulshan Yunisova
Institution: 1Koç University, Koç University Hospital, Department of Neurology, Muscle Diseases Center, Istanbul, Turkey, 2Koç University Hospital, Department of Medical Genetics&Genetic Diseases Evaluation Center, Istanbul, Turkey, 3Koç University, Koç University Hospital, Department of Pediatrics, Child Neurology Unit, Istanbul, Turkey
Introduction: Sorbitol-Dehydrogenase (SORD) is an enzyme, which converts sorbitol to fructose in carbohydrate metabolism and has been associated with diabetic neuropathy due to sorbitol deposition in axons. However, in a very recent study, SORD gene mutations that cause dysfunction in this enzyme was reported as the most common cause of autosomal recessive hereditary neuropathy.
Methods: We here report 2 additional patients from Turkey with hereditary motor neuronopathy and motor-predominant sensory-motor neuropathy phenotypes with SORD gene mutations.
Results: First patient, 35-year-old male, presented with asymmetrical and slowly progressive gait difficulty onset being at the age of 15. Neurological examination showed distal, asymmetric muscle weakness, absent deep tendon reflexes, and pes cavus deformity. Electromyography (EMG) revealed predominantly motor axonal sensori-motor polyneuropathy. Whole exome sequencing (WES) identified a homozygous pathogenic variant (c.757delG, p.Ala253fs) in SORD gene. Second patient was 16 years old male who had difficulty in walking and climbing stairs for the past 5 years. Mild symmetrical weakness predominant in peroneal muscles of distal lower extremities was found. Deep tendon reflexes were preserved with normal sensory examination. Diffuse anterior horn/anterior root involvement was revealed by EMG along with normal conduction velocities. A homozygous (c.908C>G, p.Thr303Arg) variant of uncertain significance (VUS) in SORD gene was revealed by WES. Fasting sorbitol level in serum was about 100 times increased in both patients (19.0 mg/L and 14.3 mg/L, respectively. N<0.16 mg/L).
Conclusions: SORD mutations were recently reported as one of the new, treatable cause of hereditary neuropathies. In this presentation, our aim is to point to this treatable cause of hereditary neuropathies, which presented with two distinct inherited and incurable diseases such as CMT-2 and d-HMN. The fact that there will be an effective treatment option, which can reduce sorbitol level, highlights the clinical impact of implementing next generation sequencing technologies to achieve definite diagnosis in neuromuscular disorders.
References: Yes
References 1: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S et al, Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.
References 2: SORD-related hereditary neuropathies. Fernández-Eulate G, Bruneel A, Stojkovic T. Med Sci (Paris). 2021 Nov;37 Hors série n° 1:30-31. doi: 10.1051/medsci/2021188. Epub 2021 Dec 8.
References 3: Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation. Frasquet M, Rojas-GarcÃa R, Argente-Escrig H et al, Eur J Neurol. 2021 Apr;28(4):1334-1343. doi: 10.1111/ene.14700. Epub 2021 Jan 10.
References 4: Hereditary motor neuropathies. Dohrn MF, Saporta M. Curr Opin Neurol. 2020 Oct;33(5):568-574. doi: 10.1097/WCO.0000000000000848.
Keywords: CMT, d-HMN, SORD gene, sorbitol, hereditery neuropathy, neuronopathy, WES, NGS, treatment
Poster No: 1367
Presenter: Gulshan Yunisova
Institution: 1Koç University, Koç University Hospital, Department of Neurology, Muscle Diseases Center, Istanbul, Turkey, 2Koç University Hospital, Department of Medical Genetics&Genetic Diseases Evaluation Center, Istanbul, Turkey, 3Koç University, Koç University Hospital, Department of Pediatrics, Child Neurology Unit, Istanbul, Turkey
Introduction: Sorbitol-Dehydrogenase (SORD) is an enzyme, which converts sorbitol to fructose in carbohydrate metabolism and has been associated with diabetic neuropathy due to sorbitol deposition in axons. However, in a very recent study, SORD gene mutations that cause dysfunction in this enzyme was reported as the most common cause of autosomal recessive hereditary neuropathy.
Methods: We here report 2 additional patients from Turkey with hereditary motor neuronopathy and motor-predominant sensory-motor neuropathy phenotypes with SORD gene mutations.
Results: First patient, 35-year-old male, presented with asymmetrical and slowly progressive gait difficulty onset being at the age of 15. Neurological examination showed distal, asymmetric muscle weakness, absent deep tendon reflexes, and pes cavus deformity. Electromyography (EMG) revealed predominantly motor axonal sensori-motor polyneuropathy. Whole exome sequencing (WES) identified a homozygous pathogenic variant (c.757delG, p.Ala253fs) in SORD gene. Second patient was 16 years old male who had difficulty in walking and climbing stairs for the past 5 years. Mild symmetrical weakness predominant in peroneal muscles of distal lower extremities was found. Deep tendon reflexes were preserved with normal sensory examination. Diffuse anterior horn/anterior root involvement was revealed by EMG along with normal conduction velocities. A homozygous (c.908C>G, p.Thr303Arg) variant of uncertain significance (VUS) in SORD gene was revealed by WES. Fasting sorbitol level in serum was about 100 times increased in both patients (19.0 mg/L and 14.3 mg/L, respectively. N<0.16 mg/L).
Conclusions: SORD mutations were recently reported as one of the new, treatable cause of hereditary neuropathies. In this presentation, our aim is to point to this treatable cause of hereditary neuropathies, which presented with two distinct inherited and incurable diseases such as CMT-2 and d-HMN. The fact that there will be an effective treatment option, which can reduce sorbitol level, highlights the clinical impact of implementing next generation sequencing technologies to achieve definite diagnosis in neuromuscular disorders.
References: Yes
References 1: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S et al, Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.
References 2: SORD-related hereditary neuropathies. Fernández-Eulate G, Bruneel A, Stojkovic T. Med Sci (Paris). 2021 Nov;37 Hors série n° 1:30-31. doi: 10.1051/medsci/2021188. Epub 2021 Dec 8.
References 3: Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation. Frasquet M, Rojas-GarcÃa R, Argente-Escrig H et al, Eur J Neurol. 2021 Apr;28(4):1334-1343. doi: 10.1111/ene.14700. Epub 2021 Jan 10.
References 4: Hereditary motor neuropathies. Dohrn MF, Saporta M. Curr Opin Neurol. 2020 Oct;33(5):568-574. doi: 10.1097/WCO.0000000000000848.
Keywords: CMT, d-HMN, SORD gene, sorbitol, hereditery neuropathy, neuronopathy, WES, NGS, treatment
Sorbitol-Dehydrogenase (SORD) gene Mutation as a Curable Cause of Charcot-Marie-Tooth 2 (CMT-2) and Distal Hereditary Motor Neuronopathy (d-HMN)
Poster No: 1367
Presenter: Gulshan Yunisova
Institution: 1Koç University, Koç University Hospital, Department of Neurology, Muscle Diseases Center, Istanbul, Turkey, 2Koç University Hospital, Department of Medical Genetics&Genetic Diseases Evaluation Center, Istanbul, Turkey, 3Koç University, Koç University Hospital, Department of Pediatrics, Child Neurology Unit, Istanbul, Turkey
Introduction: Sorbitol-Dehydrogenase (SORD) is an enzyme, which converts sorbitol to fructose in carbohydrate metabolism and has been associated with diabetic neuropathy due to sorbitol deposition in axons. However, in a very recent study, SORD gene mutations that cause dysfunction in this enzyme was reported as the most common cause of autosomal recessive hereditary neuropathy.
Methods: We here report 2 additional patients from Turkey with hereditary motor neuronopathy and motor-predominant sensory-motor neuropathy phenotypes with SORD gene mutations.
Results: First patient, 35-year-old male, presented with asymmetrical and slowly progressive gait difficulty onset being at the age of 15. Neurological examination showed distal, asymmetric muscle weakness, absent deep tendon reflexes, and pes cavus deformity. Electromyography (EMG) revealed predominantly motor axonal sensori-motor polyneuropathy. Whole exome sequencing (WES) identified a homozygous pathogenic variant (c.757delG, p.Ala253fs) in SORD gene. Second patient was 16 years old male who had difficulty in walking and climbing stairs for the past 5 years. Mild symmetrical weakness predominant in peroneal muscles of distal lower extremities was found. Deep tendon reflexes were preserved with normal sensory examination. Diffuse anterior horn/anterior root involvement was revealed by EMG along with normal conduction velocities. A homozygous (c.908C>G, p.Thr303Arg) variant of uncertain significance (VUS) in SORD gene was revealed by WES. Fasting sorbitol level in serum was about 100 times increased in both patients (19.0 mg/L and 14.3 mg/L, respectively. N<0.16 mg/L).
Conclusions: SORD mutations were recently reported as one of the new, treatable cause of hereditary neuropathies. In this presentation, our aim is to point to this treatable cause of hereditary neuropathies, which presented with two distinct inherited and incurable diseases such as CMT-2 and d-HMN. The fact that there will be an effective treatment option, which can reduce sorbitol level, highlights the clinical impact of implementing next generation sequencing technologies to achieve definite diagnosis in neuromuscular disorders.
References: Yes
References 1: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S et al, Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.
References 2: SORD-related hereditary neuropathies. Fernández-Eulate G, Bruneel A, Stojkovic T. Med Sci (Paris). 2021 Nov;37 Hors série n° 1:30-31. doi: 10.1051/medsci/2021188. Epub 2021 Dec 8.
References 3: Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation. Frasquet M, Rojas-GarcÃa R, Argente-Escrig H et al, Eur J Neurol. 2021 Apr;28(4):1334-1343. doi: 10.1111/ene.14700. Epub 2021 Jan 10.
References 4: Hereditary motor neuropathies. Dohrn MF, Saporta M. Curr Opin Neurol. 2020 Oct;33(5):568-574. doi: 10.1097/WCO.0000000000000848.
Keywords: CMT, d-HMN, SORD gene, sorbitol, hereditery neuropathy, neuronopathy, WES, NGS, treatment
Poster No: 1367
Presenter: Gulshan Yunisova
Institution: 1Koç University, Koç University Hospital, Department of Neurology, Muscle Diseases Center, Istanbul, Turkey, 2Koç University Hospital, Department of Medical Genetics&Genetic Diseases Evaluation Center, Istanbul, Turkey, 3Koç University, Koç University Hospital, Department of Pediatrics, Child Neurology Unit, Istanbul, Turkey
Introduction: Sorbitol-Dehydrogenase (SORD) is an enzyme, which converts sorbitol to fructose in carbohydrate metabolism and has been associated with diabetic neuropathy due to sorbitol deposition in axons. However, in a very recent study, SORD gene mutations that cause dysfunction in this enzyme was reported as the most common cause of autosomal recessive hereditary neuropathy.
Methods: We here report 2 additional patients from Turkey with hereditary motor neuronopathy and motor-predominant sensory-motor neuropathy phenotypes with SORD gene mutations.
Results: First patient, 35-year-old male, presented with asymmetrical and slowly progressive gait difficulty onset being at the age of 15. Neurological examination showed distal, asymmetric muscle weakness, absent deep tendon reflexes, and pes cavus deformity. Electromyography (EMG) revealed predominantly motor axonal sensori-motor polyneuropathy. Whole exome sequencing (WES) identified a homozygous pathogenic variant (c.757delG, p.Ala253fs) in SORD gene. Second patient was 16 years old male who had difficulty in walking and climbing stairs for the past 5 years. Mild symmetrical weakness predominant in peroneal muscles of distal lower extremities was found. Deep tendon reflexes were preserved with normal sensory examination. Diffuse anterior horn/anterior root involvement was revealed by EMG along with normal conduction velocities. A homozygous (c.908C>G, p.Thr303Arg) variant of uncertain significance (VUS) in SORD gene was revealed by WES. Fasting sorbitol level in serum was about 100 times increased in both patients (19.0 mg/L and 14.3 mg/L, respectively. N<0.16 mg/L).
Conclusions: SORD mutations were recently reported as one of the new, treatable cause of hereditary neuropathies. In this presentation, our aim is to point to this treatable cause of hereditary neuropathies, which presented with two distinct inherited and incurable diseases such as CMT-2 and d-HMN. The fact that there will be an effective treatment option, which can reduce sorbitol level, highlights the clinical impact of implementing next generation sequencing technologies to achieve definite diagnosis in neuromuscular disorders.
References: Yes
References 1: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S et al, Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.
References 2: SORD-related hereditary neuropathies. Fernández-Eulate G, Bruneel A, Stojkovic T. Med Sci (Paris). 2021 Nov;37 Hors série n° 1:30-31. doi: 10.1051/medsci/2021188. Epub 2021 Dec 8.
References 3: Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation. Frasquet M, Rojas-GarcÃa R, Argente-Escrig H et al, Eur J Neurol. 2021 Apr;28(4):1334-1343. doi: 10.1111/ene.14700. Epub 2021 Jan 10.
References 4: Hereditary motor neuropathies. Dohrn MF, Saporta M. Curr Opin Neurol. 2020 Oct;33(5):568-574. doi: 10.1097/WCO.0000000000000848.
Keywords: CMT, d-HMN, SORD gene, sorbitol, hereditery neuropathy, neuronopathy, WES, NGS, treatment
Sorbitol-Dehydrogenase (SORD) gene Mutation as a Curable Cause of Charcot-Marie-Tooth 2 (CMT-2) and Distal Hereditary Motor Neuronopathy (d-HMN)
Dr. Gulshan Yunisova
Abstract
Discussion Forum (0)
Sorbitol-Dehydrogenase (SORD) gene Mutation as a Curable Cause of Charcot-Marie-Tooth 2 (CMT-2) and Distal Hereditary Motor Neuronopathy (d-HMN)
Poster No: 1367
Presenter: Gulshan Yunisova
Institution: 1Koç University, Koç University Hospital, Department of Neurology, Muscle Diseases Center, Istanbul, Turkey, 2Koç University Hospital, Department of Medical Genetics&Genetic Diseases Evaluation Center, Istanbul, Turkey, 3Koç University, Koç University Hospital, Department of Pediatrics, Child Neurology Unit, Istanbul, Turkey
Introduction: Sorbitol-Dehydrogenase (SORD) is an enzyme, which converts sorbitol to fructose in carbohydrate metabolism and has been associated with diabetic neuropathy due to sorbitol deposition in axons. However, in a very recent study, SORD gene mutations that cause dysfunction in this enzyme was reported as the most common cause of autosomal recessive hereditary neuropathy.
Methods: We here report 2 additional patients from Turkey with hereditary motor neuronopathy and motor-predominant sensory-motor neuropathy phenotypes with SORD gene mutations.
Results: First patient, 35-year-old male, presented with asymmetrical and slowly progressive gait difficulty onset being at the age of 15. Neurological examination showed distal, asymmetric muscle weakness, absent deep tendon reflexes, and pes cavus deformity. Electromyography (EMG) revealed predominantly motor axonal sensori-motor polyneuropathy. Whole exome sequencing (WES) identified a homozygous pathogenic variant (c.757delG, p.Ala253fs) in SORD gene. Second patient was 16 years old male who had difficulty in walking and climbing stairs for the past 5 years. Mild symmetrical weakness predominant in peroneal muscles of distal lower extremities was found. Deep tendon reflexes were preserved with normal sensory examination. Diffuse anterior horn/anterior root involvement was revealed by EMG along with normal conduction velocities. A homozygous (c.908C>G, p.Thr303Arg) variant of uncertain significance (VUS) in SORD gene was revealed by WES. Fasting sorbitol level in serum was about 100 times increased in both patients (19.0 mg/L and 14.3 mg/L, respectively. N<0.16 mg/L).
Conclusions: SORD mutations were recently reported as one of the new, treatable cause of hereditary neuropathies. In this presentation, our aim is to point to this treatable cause of hereditary neuropathies, which presented with two distinct inherited and incurable diseases such as CMT-2 and d-HMN. The fact that there will be an effective treatment option, which can reduce sorbitol level, highlights the clinical impact of implementing next generation sequencing technologies to achieve definite diagnosis in neuromuscular disorders.
References: Yes
References 1: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S et al, Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.
References 2: SORD-related hereditary neuropathies. Fernández-Eulate G, Bruneel A, Stojkovic T. Med Sci (Paris). 2021 Nov;37 Hors série n° 1:30-31. doi: 10.1051/medsci/2021188. Epub 2021 Dec 8.
References 3: Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation. Frasquet M, Rojas-GarcÃa R, Argente-Escrig H et al, Eur J Neurol. 2021 Apr;28(4):1334-1343. doi: 10.1111/ene.14700. Epub 2021 Jan 10.
References 4: Hereditary motor neuropathies. Dohrn MF, Saporta M. Curr Opin Neurol. 2020 Oct;33(5):568-574. doi: 10.1097/WCO.0000000000000848.
Keywords: CMT, d-HMN, SORD gene, sorbitol, hereditery neuropathy, neuronopathy, WES, NGS, treatment
Poster No: 1367
Presenter: Gulshan Yunisova
Institution: 1Koç University, Koç University Hospital, Department of Neurology, Muscle Diseases Center, Istanbul, Turkey, 2Koç University Hospital, Department of Medical Genetics&Genetic Diseases Evaluation Center, Istanbul, Turkey, 3Koç University, Koç University Hospital, Department of Pediatrics, Child Neurology Unit, Istanbul, Turkey
Introduction: Sorbitol-Dehydrogenase (SORD) is an enzyme, which converts sorbitol to fructose in carbohydrate metabolism and has been associated with diabetic neuropathy due to sorbitol deposition in axons. However, in a very recent study, SORD gene mutations that cause dysfunction in this enzyme was reported as the most common cause of autosomal recessive hereditary neuropathy.
Methods: We here report 2 additional patients from Turkey with hereditary motor neuronopathy and motor-predominant sensory-motor neuropathy phenotypes with SORD gene mutations.
Results: First patient, 35-year-old male, presented with asymmetrical and slowly progressive gait difficulty onset being at the age of 15. Neurological examination showed distal, asymmetric muscle weakness, absent deep tendon reflexes, and pes cavus deformity. Electromyography (EMG) revealed predominantly motor axonal sensori-motor polyneuropathy. Whole exome sequencing (WES) identified a homozygous pathogenic variant (c.757delG, p.Ala253fs) in SORD gene. Second patient was 16 years old male who had difficulty in walking and climbing stairs for the past 5 years. Mild symmetrical weakness predominant in peroneal muscles of distal lower extremities was found. Deep tendon reflexes were preserved with normal sensory examination. Diffuse anterior horn/anterior root involvement was revealed by EMG along with normal conduction velocities. A homozygous (c.908C>G, p.Thr303Arg) variant of uncertain significance (VUS) in SORD gene was revealed by WES. Fasting sorbitol level in serum was about 100 times increased in both patients (19.0 mg/L and 14.3 mg/L, respectively. N<0.16 mg/L).
Conclusions: SORD mutations were recently reported as one of the new, treatable cause of hereditary neuropathies. In this presentation, our aim is to point to this treatable cause of hereditary neuropathies, which presented with two distinct inherited and incurable diseases such as CMT-2 and d-HMN. The fact that there will be an effective treatment option, which can reduce sorbitol level, highlights the clinical impact of implementing next generation sequencing technologies to achieve definite diagnosis in neuromuscular disorders.
References: Yes
References 1: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S et al, Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.
References 2: SORD-related hereditary neuropathies. Fernández-Eulate G, Bruneel A, Stojkovic T. Med Sci (Paris). 2021 Nov;37 Hors série n° 1:30-31. doi: 10.1051/medsci/2021188. Epub 2021 Dec 8.
References 3: Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation. Frasquet M, Rojas-GarcÃa R, Argente-Escrig H et al, Eur J Neurol. 2021 Apr;28(4):1334-1343. doi: 10.1111/ene.14700. Epub 2021 Jan 10.
References 4: Hereditary motor neuropathies. Dohrn MF, Saporta M. Curr Opin Neurol. 2020 Oct;33(5):568-574. doi: 10.1097/WCO.0000000000000848.
Keywords: CMT, d-HMN, SORD gene, sorbitol, hereditery neuropathy, neuronopathy, WES, NGS, treatment
Sorbitol-Dehydrogenase (SORD) gene Mutation as a Curable Cause of Charcot-Marie-Tooth 2 (CMT-2) and Distal Hereditary Motor Neuronopathy (d-HMN)
Poster No: 1367
Presenter: Gulshan Yunisova
Institution: 1Koç University, Koç University Hospital, Department of Neurology, Muscle Diseases Center, Istanbul, Turkey, 2Koç University Hospital, Department of Medical Genetics&Genetic Diseases Evaluation Center, Istanbul, Turkey, 3Koç University, Koç University Hospital, Department of Pediatrics, Child Neurology Unit, Istanbul, Turkey
Introduction: Sorbitol-Dehydrogenase (SORD) is an enzyme, which converts sorbitol to fructose in carbohydrate metabolism and has been associated with diabetic neuropathy due to sorbitol deposition in axons. However, in a very recent study, SORD gene mutations that cause dysfunction in this enzyme was reported as the most common cause of autosomal recessive hereditary neuropathy.
Methods: We here report 2 additional patients from Turkey with hereditary motor neuronopathy and motor-predominant sensory-motor neuropathy phenotypes with SORD gene mutations.
Results: First patient, 35-year-old male, presented with asymmetrical and slowly progressive gait difficulty onset being at the age of 15. Neurological examination showed distal, asymmetric muscle weakness, absent deep tendon reflexes, and pes cavus deformity. Electromyography (EMG) revealed predominantly motor axonal sensori-motor polyneuropathy. Whole exome sequencing (WES) identified a homozygous pathogenic variant (c.757delG, p.Ala253fs) in SORD gene. Second patient was 16 years old male who had difficulty in walking and climbing stairs for the past 5 years. Mild symmetrical weakness predominant in peroneal muscles of distal lower extremities was found. Deep tendon reflexes were preserved with normal sensory examination. Diffuse anterior horn/anterior root involvement was revealed by EMG along with normal conduction velocities. A homozygous (c.908C>G, p.Thr303Arg) variant of uncertain significance (VUS) in SORD gene was revealed by WES. Fasting sorbitol level in serum was about 100 times increased in both patients (19.0 mg/L and 14.3 mg/L, respectively. N<0.16 mg/L).
Conclusions: SORD mutations were recently reported as one of the new, treatable cause of hereditary neuropathies. In this presentation, our aim is to point to this treatable cause of hereditary neuropathies, which presented with two distinct inherited and incurable diseases such as CMT-2 and d-HMN. The fact that there will be an effective treatment option, which can reduce sorbitol level, highlights the clinical impact of implementing next generation sequencing technologies to achieve definite diagnosis in neuromuscular disorders.
References: Yes
References 1: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S et al, Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.
References 2: SORD-related hereditary neuropathies. Fernández-Eulate G, Bruneel A, Stojkovic T. Med Sci (Paris). 2021 Nov;37 Hors série n° 1:30-31. doi: 10.1051/medsci/2021188. Epub 2021 Dec 8.
References 3: Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation. Frasquet M, Rojas-GarcÃa R, Argente-Escrig H et al, Eur J Neurol. 2021 Apr;28(4):1334-1343. doi: 10.1111/ene.14700. Epub 2021 Jan 10.
References 4: Hereditary motor neuropathies. Dohrn MF, Saporta M. Curr Opin Neurol. 2020 Oct;33(5):568-574. doi: 10.1097/WCO.0000000000000848.
Keywords: CMT, d-HMN, SORD gene, sorbitol, hereditery neuropathy, neuronopathy, WES, NGS, treatment
Poster No: 1367
Presenter: Gulshan Yunisova
Institution: 1Koç University, Koç University Hospital, Department of Neurology, Muscle Diseases Center, Istanbul, Turkey, 2Koç University Hospital, Department of Medical Genetics&Genetic Diseases Evaluation Center, Istanbul, Turkey, 3Koç University, Koç University Hospital, Department of Pediatrics, Child Neurology Unit, Istanbul, Turkey
Introduction: Sorbitol-Dehydrogenase (SORD) is an enzyme, which converts sorbitol to fructose in carbohydrate metabolism and has been associated with diabetic neuropathy due to sorbitol deposition in axons. However, in a very recent study, SORD gene mutations that cause dysfunction in this enzyme was reported as the most common cause of autosomal recessive hereditary neuropathy.
Methods: We here report 2 additional patients from Turkey with hereditary motor neuronopathy and motor-predominant sensory-motor neuropathy phenotypes with SORD gene mutations.
Results: First patient, 35-year-old male, presented with asymmetrical and slowly progressive gait difficulty onset being at the age of 15. Neurological examination showed distal, asymmetric muscle weakness, absent deep tendon reflexes, and pes cavus deformity. Electromyography (EMG) revealed predominantly motor axonal sensori-motor polyneuropathy. Whole exome sequencing (WES) identified a homozygous pathogenic variant (c.757delG, p.Ala253fs) in SORD gene. Second patient was 16 years old male who had difficulty in walking and climbing stairs for the past 5 years. Mild symmetrical weakness predominant in peroneal muscles of distal lower extremities was found. Deep tendon reflexes were preserved with normal sensory examination. Diffuse anterior horn/anterior root involvement was revealed by EMG along with normal conduction velocities. A homozygous (c.908C>G, p.Thr303Arg) variant of uncertain significance (VUS) in SORD gene was revealed by WES. Fasting sorbitol level in serum was about 100 times increased in both patients (19.0 mg/L and 14.3 mg/L, respectively. N<0.16 mg/L).
Conclusions: SORD mutations were recently reported as one of the new, treatable cause of hereditary neuropathies. In this presentation, our aim is to point to this treatable cause of hereditary neuropathies, which presented with two distinct inherited and incurable diseases such as CMT-2 and d-HMN. The fact that there will be an effective treatment option, which can reduce sorbitol level, highlights the clinical impact of implementing next generation sequencing technologies to achieve definite diagnosis in neuromuscular disorders.
References: Yes
References 1: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Cortese A, Zhu Y, Rebelo AP, Negri S et al, Nat Genet. 2020 May;52(5):473-481. doi: 10.1038/s41588-020-0615-4. Epub 2020 May 4.
References 2: SORD-related hereditary neuropathies. Fernández-Eulate G, Bruneel A, Stojkovic T. Med Sci (Paris). 2021 Nov;37 Hors série n° 1:30-31. doi: 10.1051/medsci/2021188. Epub 2021 Dec 8.
References 3: Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation. Frasquet M, Rojas-GarcÃa R, Argente-Escrig H et al, Eur J Neurol. 2021 Apr;28(4):1334-1343. doi: 10.1111/ene.14700. Epub 2021 Jan 10.
References 4: Hereditary motor neuropathies. Dohrn MF, Saporta M. Curr Opin Neurol. 2020 Oct;33(5):568-574. doi: 10.1097/WCO.0000000000000848.
Keywords: CMT, d-HMN, SORD gene, sorbitol, hereditery neuropathy, neuronopathy, WES, NGS, treatment
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