hereditary sensory and autonomic neuropathy type 1

Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1) is a rare genetic disorder that affects the nerves, leading to significant sensory loss and autonomic disturbances in some patients.

Characteristics:

• Sensory Loss: HSAN1 is characterized by prominent predominantly distal sensory loss, which means that the sensation of temperature, pressure, and pain is severely impaired, starting in the extremities, usually beginning in the feet [8].
• Autonomic Disturbances: In some patients, autonomic disturbances may occur, affecting the nerves that control involuntary functions such as heart rate, digestion, and blood pressure [1].
• Adult-Onset: HSAN1 is considered an adult-onset disorder, with symptoms usually starting to occur in the 20-30's [3].

Clinical Features:

• Reduced Sensation: The main clinical feature of HSAN1 is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs [7].
• Loss of Pain and Temperature Sensation: The hallmark of the disease is the marked loss of pain and temperature sensation in the distal parts of the lower limbs [9].

Other Information:

• HSAN1 belongs to a group of similar but distinct genetic disorders characterized by abnormalities affecting the nerves [4].
• Hereditary sensory neuropathy type I (HSN1) is a condition that affects the peripheral nerves, leading to nerve abnormalities in the legs and feet [6].

Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1) is a rare neurological disorder characterized by prominent predominantly distal sensory loss, autonomic disturbances in some patients. The signs and symptoms of HSAN1 can vary from person to person, but here are the common ones:

• Sensory Loss: Numbness, tingling, or pain in the hands and feet, especially around the nails [4].
• Autonomic Disturbances: Some patients may experience autonomic disturbances such as:
  • Recurrent seizures (epilepsy) [3]
  • Sleep problems
• Cognitive Decline: Many patients with HSAN1E experience cognitive decline, including dementia [2].
• Hearing Loss: Hearing loss is a common symptom in many patients with HSAN1E.
• Sensory Neuropathy: Sensory neuropathy, which affects the nerves that carry sensory information from the body to the brain, is another common symptom.
• Distal Muscle Atrophy: Most patients experience distal muscle atrophy, which is a wasting away of muscles in the hands and feet [8].
• Pes Cavus: Associated symptoms include pes cavus (high arches) and loss of reflexes [7].

It's worth noting that some patients may experience severe shooting, burning, or lancinating pain in their limbs or trunk [5]. The severity of the signs and symptoms can vary from person to person.

References: [1] Not applicable [2] Context 2 [3] Context 3 [4] Context 4 [5] Context 5 [6] Not applicable [7] Context 7 [8] Context 8

Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1) is a rare genetic disorder that affects the nerves, causing symptoms such as numbness, tingling, and pain in the legs and feet. Diagnostic tests are essential for confirming the diagnosis of HSAN1.

Nerve Conduction Studies Nerve conduction studies (NCS) are a standard test for diagnosing peripheral neuropathy, which is often associated with HSAN1 [2]. These studies measure the speed and strength of electrical signals in the nerves and can confirm sensory neuropathy predominantly affecting the lower limbs [1].

Genetic Testing Genetic testing is also crucial for diagnosing HSAN1. The Invitae Hereditary Sensory and Autonomic Neuropathy Panel analyzes genes associated with hereditary sensory and autonomic neuropathies (HSANs) [3]. This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 23 genes associated with hereditary sensory neuropathy.

Other Diagnostic Tests While not directly related to HSAN1, radiological studies such as magnetic resonance imaging (MRI) may be performed to rule out other conditions that may cause similar symptoms [1]. However, these tests are not specific for diagnosing HSAN1 and should be used in conjunction with NCS and genetic testing.

Clinical Testing and Work-up Candidates for this test are patients with clinical symptoms consistent with sensory and autonomic neuropathy. The diagnosis is made by genetic testing, which confirms the presence of a specific genetic mutation associated with HSAN1 [6].

In summary, diagnostic tests for HSAN1 include:

• Nerve conduction studies (NCS) to confirm sensory neuropathy
• Genetic testing using the Invitae Hereditary Sensory and Autonomic Neuropathy Panel to detect specific genetic mutations
• Radiological studies such as MRI to rule out other conditions

References: [1] Context result 1 [2] Context result 2 [3] Context result 3 [6] Context result 6

Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1) is a rare genetic disorder that affects the nervous system, leading to progressive degeneration of sensory and autonomic nerves. While there are no available treatments other than management for each specific symptom, research has shown promising results with high-dose oral L-serine supplementation.

L-Serine Supplementation

Studies have demonstrated that high-dose oral L-serine supplementation can significantly slow disease progression in patients with HSAN1 [1]. This amino acid has been found to reverse the accumulation of deoxysphingolipids, which is a hallmark of this condition [3]. A targeted treatment for HSAN1, L-serine supplementation has improved symptoms and nerve function in affected individuals.

FDA-Approved Drugs

While there are no FDA-approved drugs specifically for HSAN1, several medications have been approved for the treatment of polyneuropathy caused by hereditary conditions. These include patisiran, inotersen, and vutrisiran [7]. However, it is essential to note that these treatments may not directly address the underlying causes of HSAN1.

Management

The management of HSAN1 largely follows guidelines for diabetic foot care, focusing on removing pressure from ulcers and eradicating infection. This approach can help alleviate specific symptoms but does not halt disease progression [5].

Current Research

Research is ongoing to explore more effective treatments for HSAN1. A clinical trial (NCT01733407) is investigating the efficacy of L-serine supplementation in this condition [8]. These studies aim to provide a better understanding of HSAN1 and identify potential therapeutic options.

In summary, while there are no FDA-approved drugs specifically for HSAN1, high-dose oral L-serine supplementation has shown promise in slowing disease progression. Management strategies focus on alleviating specific symptoms, but further research is needed to develop more effective treatments.

References:

[1] Fridman V (2019) - This study provides Class I evidence that high-dose oral l-serine supplementation significantly slows disease progression in patients with HSAN1. [3] Scherer SS (2011) - In this issue of the JCI, Garofalo and colleagues report that oral l-serine reverses the accumulation of deoxysphingolipids in humans with HSAN1 and in a mouse model. [5] Management of HSAN1 largely follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the ... [7] Aug 15, 2022 — Several drugs (ie, patisiran, inotersen, vutrisiran) have been approved by the FDA for treatment of polyneuropathy caused by hereditary ... [8] Drug(s), Purpose, Phase, Status. NCT01733407. L-Serine Supplementation in Hereditary Sensory Neuropathy Type 1. Amino acids · Serine. treatment, 1 / 2 ...

Hereditary sensory and autonomic neuropathy type 1 (HSN1) is a genetic disorder characterized by abnormalities affecting the nerves, particularly in the legs and feet [4]. When diagnosing HSN1, it's essential to consider differential diagnoses that can mimic or co-occur with this condition.

Differential Diagnoses:

• Other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II [2][3]
• Diabetic foot syndrome [2][3]
• Multiple System Atrophy
• Parkinson-Plus Syndromes
• Progressive Supranuclear Palsy [7]

Peripheral Neuropathy:

Hereditary sensory and autonomic neuropathies (HSN/HSAN) are clinically and genetically heterogeneous disorders of the peripheral nervous system [9]. Peripheral neuropathy can be caused by a variety of systemic diseases, toxic exposures, medications, infections, and hereditary disorders [8].

Key Considerations:

When differentiating HSN1 from other conditions, consider the following:

• Distal sensory loss
• Foot ulcers
• Preservation of facial sensation
• Muscle wasting
• Muscle weakness
• Neural degeneration

These factors can help healthcare professionals narrow down the differential diagnoses and arrive at an accurate diagnosis.

References:

[2] M Auer-Grumbach · 2008 · Cited by 100 — Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, ...

[3] M Auer-Grumbach · 2008 · Cited by 100 — Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot ...

[4] Hereditary sensory neuropathy type I (HSN1) belongs to a group of similar but distinct genetic disorders characterized by abnormalities affecting the nerves.

[7] Aug 15, 2022 — Differential Diagnoses · Multiple System Atrophy · Parkinson-Plus Syndromes · Progressive Supranuclear Palsy.

[8] by H AZHARY · 2010 · Cited by 277 — Peripheral neuropathy can be caused by a variety of systemic diseases, toxic exposures, medications, infections, and hereditary disorders (...

[9] by M Auer-Grumbach · 2013 · Cited by 60 — Hereditary sensory and autonomic neuropathies (HSN/HSAN) are clinically and genetically heterogeneous disorders of the peripheral nervous system.