What are the other Names for this Condition? (Also known as/Synonyms)

• Autosomal Dominant Hereditary Sensory Radicular Neuropathy, Type IA
• Hereditary Sensory and Autonomic Neuropathy Type IA (HSAN1A)
• HSN1A (Hereditary Sensory Neuropathy Type IA)

What is Hereditary Sensory Neuropathy Type IA? (Definition/Background Information)

• Hereditary Sensory Neuropathy Type IA (HSN1A) is a rare genetic condition resulting in the loss of sensation in the legs and feet
• Individuals with Hereditary Sensory Neuropathy Type IA experience peripheral nerve irregularities (peripheral neuropathy), reduced ability to feel hot or cold, and tingling or prickling (paresthesias) in the legs and feet. This can lead to painless injuries due to loss of sensations and delayed wound healing
• There is currently no known cure or preventive measures available for Hereditary Sensory Neuropathy Type IA. It can be managed symptomatically to alleviate pain and stress
• The life expectancy of an individual with HSN1A remains unaffected, but the signs and symptoms generally tend to increase over time, resulting in a gradual disability

Who gets Hereditary Sensory Neuropathy Type IA? (Age and Sex Distribution)

• Hereditary Sensory Neuropathy Type IA is a rare, congenital disorder estimated to have a prevalence of 1 per 100,000 individuals. Children are born with this condition, though the signs and symptoms may manifest only by early adolescence or into adulthood
• Both males and females are affected by HSN1A
• The condition is observed worldwide; no racial or ethnic preference is noted

What are the Risk Factors for Hereditary Sensory Neuropathy Type IA? (Predisposing Factors)

• The risk factor for Hereditary Sensory Neuropathy Type IA is inheritance of a mutation from either the mother or the father
• Only one copy of the mutation is enough to produce signs and symptoms of HSN1A (autosomal dominance)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hereditary Sensory Neuropathy Type IA? (Etiology)

• Hereditary Sensory Neuropathy Type IA is an inherited genetic disorder caused by a dominant mutation in the SPTLC1 gene located on chromosome 9, leading to the formation of certain toxic substances in the nerve cells
• SPTLC1 encodes for a subunit of a protein called serine palmitoyl transferase. This enzyme helps make sphingolipids, which are structural components of the membranes of cells
• The mutation in SPTLC1 causes a buildup of a toxic compound (deoxyspingoid base) that damages nerve cells, resulting in reduced sensations and muscle weaknesses

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Hereditary Sensory Neuropathy Type IA?

The signs and symptoms of Hereditary Sensory Neuropathy Type IA may not appear until early adolescence or adulthood, and they gradually increase as an affected individual ages. The common signs and symptoms of HSNIA include:

• Tingling and prickling sensations, numbness
• Limited ability to feel pain; mild infections or sores on the feet that may go unnoticed
• Reduced sensation to hot and cold (early sign)
• Sweaty hands and feet
• Fingertip infections
• Destruction of joints (Charcot joints)
• Drop foot
• Hearing loss
• Shooting pain (seen in the later stages)
• Muscle weakness and decreased muscle tone necessitating assistive devices, wheelchairs (after many years of signs and symptoms)

How is Hereditary Sensory Neuropathy Type IA Diagnosed?

A diagnosis of Hereditary Sensory Neuropathy Type IA may involve:

• A complete physical examination with special emphasis on neurological examination along with a screening of the patient’s medical history. The screening of family medical history is undertaken to check if relatives (other family members) have HSN1A
• Genetic testing to determine if the SPTLC1 gene is mutated
• Neurological testing (electromyography) to test nerve conductance in order to determine the extent of neuropathy
• Nerve tissue biopsy to view nerve cell deterioration: In the tissue biopsy procedure, the physician removes a sample of the tissue and sends it to the laboratory for a histopathological examination. The pathologist examines the biopsy under a microscope and arrives at a definitive diagnosis after a thorough evaluation of the clinical and microscopic findings, as well as by correlating the results of special studies on the tissues (if required)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hereditary Sensory Neuropathy Type IA?

Hereditary Sensory Neuropathy Type IA is a progressive and irreversible disorder. As an individual age, the symptoms may get worse and complications can arise. Complications of HSN1A that can occur include:

• Loss of sensations may result in repeated trauma that may go unnoticed, eventually leading to wound infections with slow healing. This may require limb amputation, in some cases
• Progressive hearing loss due to nerve damage (sensorineural deafness)
• Severe muscle weakness and deterioration, resulting in being wheelchair-bound

How is Hereditary Sensory Neuropathy Type IA Treated?

Currently, there is no treatment available for Hereditary Sensory Neuropathy Type IA. Relief from pain, symptoms, and stress of the disorder can be sought through the following measures:

• Daily inspection of feet for injuries and daily cleaning of wounds
• Routine visits to a foot care specialist
• Fusion of bone (arthrodesis) to manage pain from Charcot joints
• Ankle/foot brace (orthotic) to manage drop foot
• Anti-seizure medications to manage the shooting pain

How can Hereditary Sensory Neuropathy Type IA be Prevented?

• Currently, there are no specific methods or guidelines to prevent Hereditary Sensory Neuropathy Type IA, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Hereditary Sensory Neuropathy Type IA? (Outcomes/Resolutions)

• There is currently no known cure for Hereditary Sensory Neuropathy Type IA. However, the prognosis of the condition is usually good with appropriate follow-up and early recognition of complications
• The life expectancy of an individual with HSN1A remains unaffected, but the condition tends to progress over time, causing a gradual disability in the affected individuals

Additional and Relevant Useful Information for Hereditary Sensory Neuropathy Type IA:

Although there is currently no cure for Hereditary Sensory Neuropathy Type IA, active research is currently underway to determine ways to block toxic deoxy sphingoid bases, such as through alternative diets and gene therapy.