autosomal recessive distal hereditary motor neuronopathy 8

Autosomal Recessive Distal Hereditary Motor Neuronopathy 8 (HMNR8) Description

Autosomal recessive distal hereditary motor neuronopathy-8, also known as sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDD), is a rare genetic disorder characterized by:

• Motor axonal neuropathy: A condition where the nerve cells that control muscle movement are damaged.
• Slowly progressive distal muscle weakness: Muscle weakness mainly affecting the lower limbs, which gradually worsens over time.
• Difficulty walking and maintaining balance: As the disease progresses, individuals may experience difficulty walking, maintaining balance, and performing daily activities.

This condition is caused by mutations in the SORD gene, encoding sorbitol dehydrogenase. It is an autosomal recessive disorder, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Key Features:

• Distal muscle weakness: Primarily affecting the lower limbs.
• Motor axonal neuropathy: Damage to nerve cells controlling muscle movement.
• Slowly progressive disease course: Gradual worsening of symptoms over time.

References:

• [1] Autosomal recessive distal hereditary motor neuronopathy-8 (HMNR8), or sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDD), ...
• [5] Definition: An autosomal recessive condition caused by mutation(s) in the SORD gene, encoding sorbitol dehydrogenase. It is characterized by distal muscle ...
• [6] An autosomal recessive distal hereditary motor neuronopathy characterized by onset of distal muscle weakness mainly affecting the lower limbs and resulting ...
• [8] Definition: An autosomal recessive distal hereditary motor neuronopathy characterized by onset of distal muscle weakness mainly affecting the lower limbs ...

Initial Symptoms

The initial symptoms of Autosomal Recessive Distal Hereditary Motor Neuronopathy 8 (HMNR8) or Sorbitol Dehydrogenase Deficiency with Peripheral Neuropathy (SORDD) typically include cramps or weakness in the muscles of the big toe, which later affects the entire foot. This condition can progress over a period of approximately 5 to 10 years.

Additional Symptoms

In some cases, patients may experience distal weakness of lower limbs, hand weakness, and hoarseness. Severe distal weakness can be present as early as 6 months after birth, although motor milestones up to independent walking may still be attained. Other symptoms include:

• Foot drop
• Gait difficulties
• Axonal neuropathy seen on electrophysiologic studies
• Length-dependent motor neuropathy
• Difficulty heel-walking

Complicated Distal HMN

In some cases, unusual or additional features may be present in 'complicated' distal HMN, including predominance in the hands, vocal cord paralysis, diaphragm paralysis, and other symptoms.

These symptoms are based on information from various medical sources [1-9].

Based on the provided context, here are the diagnostic tests that can be used to diagnose autosomal recessive distal hereditary motor neuronopathy-8 (HMNR8), also known as sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDD):

• Genetic testing: This can be used to confirm a diagnosis of HMNR8, and can identify the specific genetic mutation responsible for the condition [3].
• Clinical presentation: A diagnosis of HMNR8 is typically made based on a combination of clinical features, including motor axonal neuropathy, slowly progressive distal muscle weakness mainly affecting the lower limbs, and difficulty walking or standing [4].
• Nerve conduction studies: These can be used to assess nerve function and confirm the presence of peripheral neuropathy [5].

It's worth noting that genetic testing is a key component in diagnosing HMNR8, as it can provide a definitive diagnosis and help identify affected family members. However, clinical presentation and nerve conduction studies may also play a role in making a diagnosis.

References: [3] - Context 3 [4] - Context 4 [5] - Context 5

Treatment Options for Autosomal Recessive Distal Hereditary Motor Neuronopathy 8

According to the available information, there are some potential treatment options for autosomal recessive distal hereditary motor neuronopathy 8 (dHMN-8).

• Aldose Reductase Inhibitors: Treatment of some patient fibroblasts with aldose reductase inhibitors has been explored as a potential therapeutic approach. This type of medication may help to alleviate symptoms by reducing the accumulation of toxic sugar metabolites in the body [1].
• Other Therapeutic Approaches: While there are no specific treatments mentioned for dHMN-8, researchers have investigated various other therapeutic approaches for related conditions. For example, abnormal neuromuscular transmission has been identified as a treatable target in some genetic forms of distal hereditary motor neuropathies (dHMNs) [9].

It's essential to note that these treatment options are still in the experimental stages and may not be widely available or proven effective for dHMN-8. Further research is necessary to determine the efficacy and safety of these potential treatments.

References:

[1] Context result 2: "Treatment of some patient fibroblasts with aldose reductase inhibitors..." [9] Context result 9: "...Abnormal neuromuscular transmission in some genetic forms provides a treatable target..."

The differential diagnosis for autosomal recessive distal hereditary motor neuronopathy 8 (HMNR8) involves considering other conditions that present with similar symptoms.

According to the search results, HMNR8 is characterized by onset of distal muscle weakness mainly affecting the lower limbs and resulting in difficulty walking [13]. This symptomatology can be confused with other conditions such as:

• Hereditary motor neuropathies (HMN): These are a heterogeneous group of disorders that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of HMN have minor sensory abnormalities and/or a significant upper-motor-neuron component [15].
• Charcot–Marie–Tooth disease (CMT2): This is an axonal form of CMT that can present with similar symptoms to HMNR8, including distal muscle weakness and atrophy.
• Juvenile forms of amyotrophic lateral sclerosis: These conditions can also present with similar symptoms to HMNR8, including progressive muscle weakness and atrophy.

It's worth noting that the diagnosis of HMNR8 is typically achieved through genetic testing, which can identify mutations in the SORD gene [13]. However, in cases where genetic testing is not possible or has not been performed, a differential diagnosis must be considered to rule out other conditions with similar symptomatology.