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Hereditary sensory neuropathy type I (SPTLC2)
This condition leads to progressive loss of sensation, particularly in the feet and hands, and can also cause muscle weakness. It typically begins in adolescence or early adulthood and is caused by genetic changes that disrupt lipid metabolism in nerve cells.
Overview
Hereditary Sensory Neuropathy Type I (SPTLC2), often referred to as HSAN1, is a group of inherited neurological disorders characterised by progressive degeneration of sensory and motor nerves [PMID:33671239]. This degeneration predominantly affects the longest nerves first, leading to symptoms that usually begin in the feet and gradually progress upwards to the hands and arms. The condition is considered rare, and its exact prevalence in the UK population is not well established. Over time, individuals with HSAN1 may experience significant difficulties with balance and coordination due to reduced sensation.
Symptoms & clinical features
The symptoms of Hereditary Sensory Neuropathy Type I (SPTLC2) typically emerge during adolescence or early adulthood. Initial signs often include numbness, tingling, and reduced sensation in the feet, which can make it difficult to feel pain, temperature, or touch. This loss of sensation can lead to unnoticed injuries, ulcers, and infections on the feet, sometimes resulting in bone and joint damage [PMID:26767099]. As the condition progresses, muscle weakness and wasting, particularly in the lower legs, may develop, affecting walking and balance. Hand involvement generally occurs later than foot involvement. Some individuals might also experience hearing loss or develop problems with the autonomic nervous system, which controls involuntary bodily functions like blood pressure and digestion [PMID:33671239].
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Affected organs
Hereditary Sensory Neuropathy Type I (SPTLC2) primarily affects the peripheral nervous system. This network of nerves transmits information between the brain and spinal cord and the rest of the body. Within the peripheral nervous system, the sensory nerves (responsible for touch, pain, temperature, and position sense) and motor nerves (responsible for muscle movement) are most significantly impacted. The longest nerves, those reaching the feet and hands, are typically affected first. In some cases, the inner ear (leading to hearing loss) and elements of the autonomic nervous system may also be involved.
Risks & severity
The severity of Hereditary Sensory Neuropathy Type I (SPTLC2) can vary among affected individuals, even within the same family. Symptoms usually begin in the second or third decade of life, although onset can range from childhood to middle age. The progressive loss of sensation increases the risk of unnoticed injuries, infections, and bone deformities, particularly in the feet. These complications can sometimes lead to the need for amputation if severe infections develop. While the condition is progressive, it generally does not affect life expectancy. Regular monitoring and proactive management are crucial to reduce complications and maintain quality of life.
Genetic causes
Hereditary Sensory Neuropathy Type I (SPTLC2) is caused by pathogenic variants in the SPTLC2 gene. This gene provides instructions for making a protein that is part of an enzyme called serine palmitoyltransferase (SPT). SPT plays a crucial role in the first step of sphingolipid synthesis [PMID:26767099]. Sphingolipids are a class of lipids (fats) that are essential components of cell membranes, particularly abundant in nerve cells, where they contribute to the myelin sheath that insulates nerve fibres. Pathogenic variants in SPTLC2 can lead to a change in the enzyme's function, causing it to produce atypical and toxic sphingolipid-like compounds. These toxic compounds are believed to accumulate in nerve cells, particularly sensory neurons, leading to their damage and degeneration, resulting in the symptoms observed in HSAN1.
Inheritance pattern
Hereditary Sensory Neuropathy Type I (SPTLC2) is inherited in an autosomal dominant pattern. This means that an individual only needs to inherit one copy of the altered SPTLC2 gene from one parent to develop the condition. If one parent has the condition, there is a 50% chance with each pregnancy that their child will inherit the altered gene and therefore be affected. This pattern applies equally to male and female offspring. Individuals who do not inherit the altered gene will not develop the condition and cannot pass it on to their children.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
A diagnosis of Hereditary Sensory Neuropathy Type I (SPTLC2) is typically suspected based on characteristic clinical symptoms, such as progressive sensory loss and muscle weakness, particularly in the feet and hands, with onset in adolescence or early adulthood. Nerve conduction studies and electromyography (NCS/EMG) can help confirm peripheral nerve damage. A definitive diagnosis is established through genetic testing to identify a pathogenic variant in the SPTLC2 gene. In the UK, genetic testing for inherited neuropathies, including HSAN1, falls under the NHS Genomic Medicine Service. A clinical geneticist or neurologist would typically refer individuals for testing, often guided by specific R-codes for neuropathies, such as R301 'Inherited Peripheral Neuropathy'. Genetic counsellors play an important role in explaining the testing process, results, and implications for families.
Management & lifestyle
While there is currently no cure for Hereditary Sensory Neuropathy Type I (SPTLC2), management focuses on alleviating symptoms, preventing complications, and improving quality of life. Regular foot care is paramount to prevent and manage ulcers and infections, and may involve podiatry services. Physiotherapy and occupational therapy can help maintain mobility, strength, and independence. Pain management strategies may be employed for neuropathic pain. Audiology services can assess and manage any hearing loss. In the UK, individuals are typically managed through a multidisciplinary team within the NHS, often coordinated by a neurologist. Genetic counselling is also recommended to discuss the genetic implications for the individual and their family members.
UK care pathway
In the UK, individuals suspected of having Hereditary Sensory Neuropathy Type I (SPTLC2) would typically be referred by their GP to a neurologist. If an inherited neuropathy is suspected, the neurologist may then refer the individual to a clinical genetics service. This service can facilitate genetic testing through the NHS Genomic Medicine Service, often using specific R-codes relevant to inherited neuropathies like R301. Genetic counsellors within these services provide vital support, offering information about the condition, inheritance patterns, and implications for family planning, helping patients navigate their diagnostic and management journey.
Frequently asked questions
Will my children inherit Hereditary Sensory Neuropathy Type I (SPTLC2)?
Because Hereditary Sensory Neuropathy Type I (SPTLC2) is inherited in an autosomal dominant pattern, if you have the condition, each of your children has a 50% chance of inheriting the altered gene and developing the condition. Genetic counselling can provide more personalised information.
When do symptoms of Hereditary Sensory Neuropathy Type I (SPTLC2) usually start?
Symptoms typically begin during adolescence or early adulthood, often in the second or third decade of life. However, the age of onset can vary, sometimes appearing in childhood or later in middle age.
Can Hereditary Sensory Neuropathy Type I (SPTLC2) be cured?
Currently, there is no cure for Hereditary Sensory Neuropathy Type I (SPTLC2). Treatment focuses on managing symptoms, preventing complications, and supporting individuals to maintain their quality of life. Research into potential therapies is ongoing.
What kind of doctors will I see for Hereditary Sensory Neuropathy Type I (SPTLC2)?
You will likely be seen by a neurologist, who specialises in conditions of the nervous system. You may also see a podiatrist for foot care, a physiotherapist for mobility, and a genetic counsellor for information about the genetic aspects of the condition and its inheritance.
How does Hereditary Sensory Neuropathy Type I (SPTLC2) affect daily life?
The progressive loss of sensation and muscle weakness can impact daily activities such as walking, balance, and fine motor skills. Careful foot care is essential to prevent injuries, and adaptive strategies may be needed to manage tasks affected by reduced sensation.