atypical hereditary sensory neuropathy

Atypical Hereditary Sensory Neuropathy (AHSN) Description

Atypical Hereditary Sensory Neuropathy, also known as AHSN, is a rare genetic disorder characterized by late-onset sensory ataxia without ulcerating acropathy or autonomic abnormalities [1][2]. This condition affects the peripheral nerves, leading to impaired sensation and coordination in the limbs.

Key Features:

• Late onset of symptoms, typically occurring in adulthood
• Sensory ataxia, which is a loss of coordination and balance due to sensory impairment
• Absence of ulcerating acropathy (a condition where skin ulcers form on the extremities) and autonomic abnormalities [3]
• Hereditary nature, meaning it is passed down from parents to offspring

Other Relevant Information:

AHSN has been reported in a few cases, including a study by Staal and Mechelse that described two brothers with late-onset sensory ataxia without ulcerating acropathy or autonomic abnormality [4]. The Disease Ontology Definition also describes AHSN as a hereditary sensory neuropathy characterized by late onset of sensory ataxia without ulcerating acropathy or autonomic abnormalities [5].

References:

[1] Context result 1 [2] Context result 6 [3] Context result 4 [4] Context result 7 [5] Context result 8

Common Signs and Symptoms

Atypical hereditary sensory neuropathy (HSN) can manifest in various ways, but the following symptoms are commonly reported:

• Sensory alterations: Patients may experience progressive sensory loss, numbness, tingling, or pain in their limbs [7].
• Muscle wasting: Muscle atrophy, particularly in the distal muscles of the hands and feet, is a common feature [8].
• Weakness: Gradual weakness and loss of muscle bulk are often observed, especially in the lower extremities [1].
• Loss of sensation: Patients may experience diminished or absent reflexes, mild proprioceptive deficit with preserved pinprick/light touch, and loss of pain sensation [5].
• Dysautonomia: Orthostatic hypotension, temperature dysregulation, and pupil dilation are often noted in these patients [6].

Other Possible Symptoms

In some cases, atypical HSN may also present with:

• Throat clearing
• Hoarse voice
• Cough syncope
• Sensorineural hearing loss [4]
• Rhythmic shaking (tremors) [3]

It's essential to note that the symptoms of atypical HSN can vary widely among individuals, and not everyone may experience all of these signs. A thorough medical evaluation is necessary for an accurate diagnosis.

References: [1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8

Diagnostic Tests for Atypical Hereditary Sensory Neuropathy (HMSN/ACC)

Atypical Hereditary Sensory Neuropathy (HMSN/ACC) is a rare genetic disorder that affects the peripheral nerves. Diagnosing this condition can be challenging, but several diagnostic tests can help establish a diagnosis.

Laboratory Tests

• Genetic testing: This is a crucial test for diagnosing HMSN/ACC. A genetic etiology of peripheral neuropathy is typically suggested by biallelic pathogenic variants in SLC12A6 [1].
• CSF examination: Cerebrospinal fluid (CSF) examination can help rule out other conditions that may cause similar symptoms.
• Nerve imaging: Imaging tests such as MRI or CT scans can help visualize the nerves and identify any abnormalities.
• Nerve biopsy: A nerve biopsy can provide a sample of nerve tissue for further analysis.

Other Diagnostic Tests

• Autonomic testing: Autonomic dysfunction is challenging to identify on examination, so autonomic testing may be indicated [4].
• Electrophysiologic studies: These studies can help confirm the diagnosis by showing primarily axonal sensory and often motor peripheral neuropathy [8].
• Electromyography (EMG) and motor nerve conduction tests: These tests can help clinicians decide what type of motor and sensory neuropathy it is and how to proceed with treatment.

Next-Generation Sequencing (NGS)

A comprehensive testing approach using next-generation sequencing (NGS) can help establish whether a peripheral neuropathy is genetic in nature [5]. This test can identify the specific genetic mutation responsible for HMSN/ACC.

In summary, diagnosing atypical hereditary sensory neuropathy requires a combination of laboratory tests, including genetic testing, CSF examination, nerve imaging, and nerve biopsy. Other diagnostic tests such as autonomic testing, electrophysiologic studies, EMG, and motor nerve conduction tests can also provide valuable information.

References: [1] C Gauvreau (2020) - Diagnosis/testing [2] HC Lehmann (2020) - Laboratory tests, including genetic testing, CSF examination, nerve imaging, and nerve biopsy [3] G Castelli (2020) - Autonomic testing may be indicated because dysfunction is challenging to identify on examination. [4] Y Chen - CMT is a genetic heterogenous disorder. Genetic testing is a key in confirming the disease, determining a mode of inheritance and identifying associated...

Based on the available information, it appears that there are limited treatment options for atypical hereditary sensory neuropathy.

• Rituximab: One study suggests that rituximab may be effective in treating DADS-M (a subtype of atypical hereditary sensory neuropathy), with a favorable response observed [2].
• Gabapentin and antidepressants: In patients with atypical TN, both gabapentin and antidepressants are expected to be efficacious and should be tried as an add-on to other treatments [3].
• Other treatments: While there are no effective treatments for hereditary neuropathies in general, symptomatic treatments such as physiotherapy, analgesics, or surgery may be used to manage symptoms [5].

It's worth noting that gene therapies and other experimental treatments have been explored in rodent models, but their clinical benefit is unclear [7]. Additionally, a study on high-dose oral l-serine supplementation found significant slowing of disease progression in patients with HSAN1 (a subtype of hereditary sensory neuropathy) [8].

However, it's essential to consult with a healthcare professional for medical advice and treatment, as they can provide personalized guidance based on individual circumstances [6].

Differential Diagnosis of Atypical Hereditary Sensory Neuropathy

Atypical hereditary sensory neuropathy refers to a condition where the symptoms and presentation do not fit the typical characteristics of hereditary motor and sensory neuropathy (HMSN) or Charcot-Marie-Tooth disease (CMT). In such cases, differential diagnosis is crucial to identify the underlying cause.

Possible Differential Diagnoses:

• Other Hereditary Sensory and Autonomic Neuropathies (HSAN): Conditions like HSAN II, which can present with similar symptoms to HMSN or CMT.
• Diabetic Foot Syndrome: A complication of diabetes that can lead to sensory neuropathy.
• Alcoholic Neuropathy: Damage to the nerves due to excessive alcohol consumption.
• Neuropathies caused by other neurotoxins/drugs: Exposure to certain toxins or medications can cause peripheral neuropathy.
• Immune Mediated Neuropathy: Conditions like Guillain-Barré syndrome, where the immune system attacks the nerves.
• Amyloidosis: A condition where abnormal proteins accumulate in the nerves and other tissues.
• Spinal Cord Diseases: Conditions affecting the spinal cord, such as tabes dorsalis or lepra neuropathy.

Key Considerations:

• Family History: Emphasized in arriving at the correct diagnosis, especially for hereditary conditions.
• Physical Evaluation: A thorough examination to look for muscle atrophy, weakness, and sensory deficits.
• Genetic Testing: May be necessary to confirm a diagnosis of HMSN or CMT, and to rule out other genetic conditions.

References:

• [3] Hereditary motor sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth Disease (CMT), is the most commonly inherited peripheral polyneuropathy.
• [13] Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours.
• [12] Differential diagnoses that should be considered include: ... Literature suggests that idiopathic sensory neuropathy is a diagnosis of exclusion and that there may be an autoimmune component of the pathophysiology.