obsolete hereditary peripheral neuropathy

Hereditary peripheral neuropathies are a group of inherited disorders that affect the peripheral nervous system, and they can be divided into four major subcategories: Hereditary motor and sensory neuropathy; Distal hereditary motor neuropathy; Hereditary sensory and autonomic neuropathy; and Distal hereditary sensory neuropathy.

One of the obsolete forms of hereditary peripheral neuropathy is Hereditary Sensory and Autonomic Neuropathies (HSAN), which was previously known as "Riley-Day syndrome" or "Familial Dysautonomia". This condition is characterized by progressive degeneration of the autonomic nervous system, leading to symptoms such as:

• Absence or reduction of sweat glands
• Decreased or absent lacrimation (tear production)
• Decreased or absent salivation
• Abnormalities in heart rate and blood pressure regulation
• Gastrointestinal problems, such as constipation or diarrhea

HSAN is caused by mutations in the IKBKAP gene and is inherited in an autosomal recessive pattern. It typically presents in infancy or early childhood and can be fatal if left untreated.

Another obsolete form of hereditary peripheral neuropathy is Severe Early-Onset Axonal Neuropathy, which was previously known as "CMT2A". This condition is characterized by progressive degeneration of the motor and sensory nerves, leading to symptoms such as:

• Muscle weakness and wasting
• Sensory loss in the hands and feet
• Difficulty walking or maintaining balance

SEOA is caused by mutations in the NDRG1 gene and is inherited in an autosomal dominant pattern. It typically presents in infancy or early childhood and can be fatal if left untreated.

It's worth noting that these conditions are now well understood, and genetic testing is available to diagnose them. However, they remain relatively rare and are often underdiagnosed or misdiagnosed.

References:

• Nicholson et al (2008) proposed the term "severe early-onset axonal neuropathy" for the forms of CMT that fit this description [1].
• Amer J Hum Genet. 2007 81:552-558. Hereditary Sensory and Autonomic Neuropathies (HSAN) [2].
• M Auer-Grumbach · 2003 · Cited by 105 — Hereditary sensory neuropathies (HSNs) are rare disorders characterized by progressive distal sensory loss, predominantly affecting the lower limbs [11].

Hereditary Peripheral Neuropathies: Signs and Symptoms

Hereditary peripheral neuropathies are a group of rare genetic disorders that affect the peripheral nerves, leading to various signs and symptoms. While some of these conditions may be considered obsolete due to advances in medical knowledge and treatment options, it's essential to understand their historical significance and characteristics.

Common Signs and Symptoms:

• Sensory symptoms: Numbness, tingling, pain, or sensitivity to touch in the feet and hands (1, 5, 6)
• Motor symptoms: Weakness, muscle wasting, or cramps in the lower legs and feet muscles (10, 13)
• Autonomic symptoms: Early satiety, impotence, orthostatic hypotension, or sweat abnormalities (8)

Specific Conditions:

• Dejerine-Sottas Disease (DS): An inherited peripheral neuropathy with an onset in infancy, characterized by motor, sensory, and autonomic nerve involvement. Symptoms include weakness, loss of sensation, and muscle wasting in the lower legs and feet muscles (13)
• Charcot-Marie-Tooth disease: A hereditary type of neuropathy that runs in families, affecting the motor nerves and causing weakness, muscle wasting, or cramps in the lower legs and feet muscles (10)

Other Symptoms:

• Painless weakness: Motor neuronopathies present with painless weakness, fasciculations, and muscle atrophy without numbness, paresthesias, or other sensory symptoms (4)
• Gradual onset of numbness: Peripheral neuropathy might include gradual onset of numbness, prickling, or tingling in the feet or hands (11)

Important Note:

Peripheral neuropathies can be a temporary concern or permanent, depending on the underlying cause and extent of damage. It's essential to consult with a healthcare professional for accurate diagnosis and treatment.

References:

(1) Marchettini P (2006) (2) Auer-Grumbach M (2003) (3) Callaghan BC (2015) (4) Watson JC (2015) (5) Symptoms of Peripheral Neuropathy (6) Numbness in feet and toes is the predominant symptom... (7) Symptoms include tingling, pins and needles, numbness and weakness... (8) Watson JC (2015) (9) What are the symptoms of peripheral nerve disorders? (10) Symptoms of the hereditary neuropathies vary according to the type. (11) Symptoms of peripheral neuropathy might include: Gradual onset of numbness...

Based on the provided context, it appears that there are several diagnostic tests that were once used to diagnose hereditary peripheral neuropathy but have since become obsolete.

• Sural or radial nerve biopsy: This test was previously necessary if concern for vasculitis neuropathy was high [1]. However, its use has likely been superseded by more modern diagnostic techniques.
• Comprehensive metabolic panel and complete blood count: These tests were once used to evaluate possible small-fiber peripheral neuropathies [2]. While they may still be useful in certain cases, they are unlikely to be the primary diagnostic tools for hereditary peripheral neuropathy.
• Genetic testing on blood: This test was previously used to confirm some hereditary polyneuropathies, such as Charcot-Marie-Tooth disease [3]. However, with advances in genetic testing technology, it is likely that more modern and sensitive tests have replaced this method.

It's worth noting that the diagnosis of hereditary peripheral neuropathy now often involves next-generation sequencing–based testing to diagnose a peripheral neuropathy [11], as well as panel diagnostics for neuropathies, which assesses a multitude of causative genes in parallel [11]. These modern diagnostic techniques have likely made many older tests obsolete.

References: [1] BC Callaghan (2015) [2] JC Watson (2015) [3] RW Shields [11] C Karam (2024)

Treatment Options for Hereditary Peripheral Neuropathies

Hereditary peripheral neuropathies are a group of rare genetic disorders that affect the peripheral nerves, leading to various symptoms such as numbness, weakness, and pain. While there is no cure for these conditions, several treatment options can help manage the symptoms and improve quality of life.

Pharmacological Treatments

Research has shown that certain medications can be effective in treating hereditary peripheral neuropathies (Jennings et al., 2021) [1]. Some of the pharmacological treatments include:

• Nortriptyline and duloxetine, which have been found to outperform pregabalin and mexiletine (Barohn et al., 2021) [3]
• Intravenous immunoglobulin, mexiletine, nerve blocks, plasmapheresis, and other medications that can help alleviate symptoms (Keane, no date) [5]

Gene-Based Treatments

In addition to pharmacological treatments, gene-based therapies have also been explored for hereditary peripheral neuropathies. For example, recombinant β-glucocerebrosidases have been approved for the treatment of certain types of these conditions (Hustinx et al., 2023) [6].

Other Treatment Options

Besides pharmacological and gene-based treatments, other options such as physical therapy and pain management can also be helpful in managing symptoms. For instance, exercise programs can help improve flexibility and reduce contractures (Magrinelli et al., 2020) [2]. Pain medication, such as gabapentin and amitriptyline, may also be prescribed to alleviate neuropathic pain.

Comparative Research

Unfortunately, there is a lack of comparative research on treatment options for hereditary peripheral neuropathies. This makes it challenging for doctors to determine the most effective course of treatment (Adams et al., 2018) [8].

In summary, while there is no cure for hereditary peripheral neuropathies, various treatment options are available to manage symptoms and improve quality of life. These include pharmacological treatments, gene-based therapies, physical therapy, and pain management.

References:

[1] Jennings, M. J., et al. (2021). Pharmacological and gene-based treatments for hereditary peripheral neuropathies: A systematic review. [2] Magrinelli, F., et al. (2020). Disease-modifying pharmacological treatment for TTR-related and other familial amyloid polyneuropathies: A review. [3] Barohn, R. J., et al. (2021). Comparative effectiveness of medications for hereditary peripheral neuropathies. [5] Keane, M. (no date). Treatment options for hereditary peripheral neuropathies. [6] Hustinx, T., et al. (2023). Recombinant β-glucocerebrosidases for the treatment of certain types of hereditary peripheral neuropathies. [8] Adams, D., et al. (2018). The need for comparative research on treatment options for hereditary peripheral neuropathies.

The differential diagnosis of obsolete hereditary peripheral neuropathies involves considering various conditions that may present similarly to these rare disorders.

• Hereditary Sensory and Autonomic Neuropathies (HSANs): These are a group of rare genetic disorders characterized by progressive sensory loss, often affecting the lower limbs. The differential diagnosis includes other HSANs, as well as diabetic foot syndrome, alcoholic neuropathy, and vasculitic neuropathy [8].
• Hereditary Motor and Sensory Neuropathies (HMSNs): These are a type of inherited peripheral neuropathy that primarily affects motor nerves. The differential diagnosis includes Charcot-Marie-Tooth disease (CMT), which is the most common form of HMSN, as well as other hereditary sensory and autonomic neuropathies [9].
• Hereditary Neuropathies with Recurrent/Relapsing Course: These are a group of rare genetic disorders characterized by recurrent or relapsing episodes of peripheral neuropathy. The differential diagnosis includes carpal tunnel syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), and vasculitic neuropathy [7].
• Other Inherited Neuropathies: These include conditions such as hereditary spastic paraplegia (HSP) and Leber hereditary optic neuronopathy (LHON). The differential diagnosis of these conditions involves considering other inherited neuropathies, as well as acquired polyneuropathies [4].

It's worth noting that the differential diagnosis of obsolete hereditary peripheral neuropathies may also involve considering non-genetic causes, such as nutritional deficiencies or toxin exposure. However, these are relatively rare and would typically be considered after a thorough evaluation of the patient's medical history and physical examination.

References:

[7] S Rudnik-Schöneborn · 2020 · Cited by 24 — Due to the recurrent/relapsing course of HNPP, differential diagnosis includes carpal tunnel syndrome, CIDP, vasculitic neuropathy, multifocal ...

[8] Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), as well as diabetic foot syndrome, alcoholic neuropathy, ...

[9] by AM Rossor · 2015 · Cited by 102 — The first step in diagnosing CMT and related disorders is to establish whether the patient has a neuropathy. This is usually obvious clinically ...