obsolete sorbitol dehydrogenase deficiency with peripheral neuropathy

Definition and Characteristics

Obsolete sorbitol dehydrogenase deficiency with peripheral neuropathy, also known as DOID:0081376, is a neuromuscular disease characterized by the onset of distal muscle weakness mainly affecting the lower limbs. This condition results in difficulty walking and other mobility issues.

• The disease is associated with a deficiency in sorbitol dehydrogenase, an enzyme that plays a crucial role in the metabolism of sugars.
• Peripheral neuropathy, a type of nerve damage, is also a key feature of this condition.

Causes and Associations

The disease has been linked to hereditary neuropathy, suggesting a genetic component. A mutation in the SORD gene, which codes for sorbitol dehydrogenase, has been identified as a cause of this condition.

• The increased levels of sorbitol and mannitol, two sugars that accumulate due to the enzyme deficiency, may contribute to the development of peripheral neuropathy.
• This disease is considered obsolete, indicating that it is no longer a commonly diagnosed or studied condition.

References

• [1] A neuromuscular disease that is characterized by onset of distal muscle weakness mainly affecting the lower limbs and resulting in difficulty walking and ... (Search result 1)
• [5] Definition: A neuromuscular disease that is characterized by onset of distal muscle weakness mainly affecting the lower limbs and resulting in difficulty walking and ... (Search result 5)
• [7] Description: A neuromuscular disease that affects the peripheral nerves, leading to muscle weakness and mobility issues. (Search result 7)
• [9] Description: A neuromuscular disease that is characterized by distal muscle weakness and peripheral neuropathy. (Search result 9)

Clinical symptoms associated with DPN (Diabetic Peripheral Neuropathy) involve poor gait and balance, while abnormal cold and/or heat sensation are linked to large sensory fibers.

• Poor gait and balance: This is a common symptom of DPN, which can lead to falls and injuries.
• Abnormal sensations: Patients with DPN may experience numbness, tingling, or burning sensations in their feet and legs, making it difficult to walk or stand for long periods.

In addition to these symptoms, patients with sorbitol dehydrogenase deficiency may also experience:

• Painful positive symptoms: These include squeezing, throbbing, freezing, burning, or lancinating sensations.
• Non-painful positive symptoms: Patients may experience a range of non-painful sensations, such as numbness or tingling.

The accumulation of sorbitol and fructose in nerve cells has been shown to decrease (Na+/ K+)-ATPase activity, leading to further complications.

• Decreased ATPase activity: This can lead to a range of problems, including muscle weakness, fatigue, and impaired nerve function.
• Complications: The accumulation of sorbitol and fructose in nerve cells can also lead to other complications, such as kidney damage and vision problems.

References:

1. by KL Farmer · 2012 · Cited by 148 — Clinical symptoms associated with DPN involve poor gait and balance associated with large sensory fibers and abnormal cold and/or heat sensation associated with ...
2. by AN Ligezka · 2021 · Cited by 43 — Given that SORD (sorbitol dehydrogenase) deficiency has been linked to hereditary neuropathy our findings suggest that the increased sorbitol and mannitol ...
3. by D Mahmood · 2009 · Cited by 75 — [6] The symptoms of DN depend upon the type of neuropathy and the nerves affected. Some patients remain asymptomatic, while others may manifest symptoms such as ...
4. by S Flores — DN may produce painful positive symptoms like squeezing, throbbing, freezing, burning, or lancinating sensations. Non-painful positive symptoms include a ...
5. Accumulation of sorbitol and fructose in nerve cells has been shown to decrease (Na+/ K+)-ATPase activity.
6. by M Hustinx · 2023 · Cited by 1 — The management of inherited neuropathies relies mostly on the treatment of symptoms. In recent years, a better understanding of the pathogenic mechanisms ...
7. Dec 4, 2005 — Fructose is also a byproduct of polyol-path- way activation via the sorbitol dehydrogenase-driv- ... or reverse the signs and symptoms of diabetic ...
8. by AI Vinik · 2004 · Cited by 543 — Patients with neuropathic pain usually present with both. Absence of pain sometimes may not be caused by improvement in neuropathy, but to a consequence of ...
9. The clinical symptoms and signs, which may appear either abruptly or insidiously, consist of malaise, fever, sweating, tachycardia, and abdominal and joint pain ...
10. Diabetic neuropathy is not a single entity but a number of different syndromes with subclinical or clinical manifestations depending on the classes of nerve ...

Diagnostic Tests for Sorbitol Dehydrogenase Deficiency with Peripheral Neuropathy

Sorbitol dehydrogenase (SORD) deficiency is a genetic condition that causes a progressive peripheral neuropathy. Diagnosing this condition requires specific tests to detect the presence of sorbitol and xylitol in the urine, as well as molecular analysis of the SORD gene.

• Urine Assay: The preferred test for assessing sorbitol dehydrogenase deficiency-related peripheral neuropathy is a urine assay that measures the levels of sorbitol and xylitol. This test is specific to this condition and can help diagnose it accurately.
• Molecular Analysis: Molecular analysis of the SORD gene is also recommended to confirm the diagnosis. However, due to the presence of the SORD2P pseudogene, specific molecular testing approaches may be required.

Key Information

• Patient's age is a necessary piece of information for these tests.
• A positive test result is diagnostic of sorbitol dehydrogenase deficiency-related neuropathy.
• Molecular analysis should follow up with a urine assay to confirm the diagnosis.

References

[1] This is the preferred test for assessing sorbitol dehydrogenase (SORD) deficiency-related peripheral neuropathy. The preferred test for monitoring effectiveness of treatment in patients with phosphomannomutase 2 deficiency (PMM2-CDG) is SORBU / Sorbitol and Mannitol, Quantitative, Random, Urine. Necessary Information. 1. Patient’s age is ... [5] [12] A positive test result is diagnostic of sorbitol dehydrogenase (SORD) deficiency-related neuropathy; however, it is strongly recommended to follow-up with molecular analysis. [13] This is the preferred test for monitoring effectiveness of treatment in patients with phosphomannomutase 2 deficiency (PMM2-CDG). The preferred test for assessing sorbitol dehydrogenase (SORD) deficiency-related peripheral neuropathy is SORD / Sorbitol and Xylitol, Quantitative, Random, Urine. Necessary Information. Patient's age is required. [14] This is the preferred test for monitoring effectiveness of treatment in patients with phosphomannomutase 2 deficiency (PMM2-CDG). The preferred test for assessing sorbitol dehydrogenase (SORD) deficiency-related peripheral neuropathy is SORD / Sorbitol and Xylitol, Quantitative, Random, Urine. Necessary Information. Patient's age is required.

Treatment Options for Obsolete Sorbitol Dehydrogenase Deficiency with Peripheral Neuropathy

Peripheral neuropathy caused by obsolete sorbitol dehydrogenase deficiency is a rare condition that affects the nerves. While there are no specific FDA-approved medications for this condition, treatment options can be considered based on the underlying cause and symptoms.

• Removing the offending agent: If the peripheral neuropathy is caused by a drug-induced reaction, removing the offending agent from the system may help alleviate symptoms [9].
• Aldose reductase inhibitors: Although not specifically approved for obsolete sorbitol dehydrogenase deficiency, aldose reductase inhibitors like sorbinil have been studied as potential treatments for diabetic peripheral neuropathy, which shares some similarities with this condition [3][10].

It's essential to note that treatment options may vary depending on the individual case and the severity of symptoms. Consultation with a healthcare professional is necessary to determine the best course of action.

Current FDA-approved medications: While not specifically approved for obsolete sorbitol dehydrogenase deficiency, medications like duloxetine and pregabalin are considered first-line treatments for pain related to diabetic peripheral neuropathy [6][8].

References: [3] Context 3 [9] Context 9 [10] Context 10

Differential Diagnosis of Sorbitol Dehydrogenase Deficiency with Peripheral Neuropathy

Sorbitol dehydrogenase (SORD) deficiency is a rare genetic disorder that can lead to peripheral neuropathy, a condition characterized by damage to the peripheral nerves. The differential diagnosis of SORD deficiency involves ruling out other conditions that may present with similar symptoms.

Conditions to Consider:

• Diabetic Neuropathy (DN): DN is a group of syndromes resulting from disturbances in nerve function caused by diabetes mellitus [6]. While DN and SORD deficiency can both cause peripheral neuropathy, they have distinct underlying causes.
• Vitamin B1 Deficiency: A vitamin B1 (thiamine) deficiency is known to be a factor in peripheral neuropathy [8]. This condition should be considered in the differential diagnosis of SORD deficiency, particularly if there are signs of malnutrition or other vitamin deficiencies.
• SORD Deficiency: Mutations on the SORD gene can impair production of Sorbitol Dehydrogenase, an enzyme that processes sorbitol. This condition is similar to SORD deficiency and should be considered in the differential diagnosis [9].
• Other Genetic Disorders: Other genetic disorders, such as hereditary neuropathy with liability to pressure palsies (HNPP), can also present with peripheral neuropathy. These conditions should be ruled out through genetic testing and other diagnostic procedures.

Diagnostic Criteria:

To diagnose SORD deficiency, the following criteria should be met:

• Genetic Testing: Genetic testing for mutations on the SORD gene is essential to confirm the diagnosis.
• Clinical Evaluation: A thorough clinical evaluation, including a review of medical history and physical examination, is necessary to rule out other conditions that may present with similar symptoms.
• Laboratory Tests: Laboratory tests, such as measurement of sorbitol levels in urine or blood, can help confirm the diagnosis.

References:

[1] S Flores. Diabetic neuropathy (DN) is a group of syndromes resulting from the disturbances in nerve function caused by diabetes mellitus. [2] M Hustinx. Here, we systematically review the therapies that have emerged in this field over the last five years. [3] Oct 15, 2021. Given that SORD (sorbitol dehydrogenase) deficiency has been linked to hereditary neuropathy our findings suggest that the increased sorbitol and mannitol ... [4] by KL Farmer · 2012 · Cited by 148 — Clinical symptoms associated with DPN involve poor gait and balance associated with large sensory fibers and abnormal cold and/or heat sensation associated with ... [5] Accumulation of sorbitol and fructose in nerve cells has been shown to decrease (Na+/ K+)-ATPase activity. [6] by S Flores — Diabetic neuropathy (DN) is a group of syndromes resulting from the disturbances in nerve function caused by diabetes mellitus1. [7] by M Hustinx · 2023 · Cited by 1 — Here, we systematically review the therapies that have emerged in this field over the last five years. An updated list of diseases with peripheral neuropathy as ... [8] Dec 4, 2005 — A vitamin B1 (thiamine) deficiency, which can be due to various underlying causes, is known to be a factor in peripheral neuropathy. [9] Feb 28, 2023 — SORD Deficiency is similar. Mutations on the SORD gene can impair production of Sorbitol Dehydrogenase, an enyme that processes sorbitol. [10] Oct 18, 2024 — P004: Urine polyols for diagnosis of sorbitol dehydrogenase (SORD) deficiency-related peripheral neuropathy*. Article. Jan 2024. Amy ...