Hereditary Neuropathy: What's That?

Today's post from ghr.nlm.nih.gov (see link below) looks at a rare form of neuropathy (1 or 2 in 100,000) that still shares the same symptoms as most other forms. If you Google neuropathy you may well come across several articles about hereditary neuropathy and may start to wonder if that's what you have. This article helps to clear up why it's most likely that your form of neuropathy stems from another source. Basically, hereditary neuropathy happens as a result of an inherited genetic abnormality but the problems you may face from the diagnosis on, are much the same as most people having to live with the disease and what's important is how those symptoms are treated to reduce their impact on your life.
 

What is hereditary sensory neuropathy type IA?
Reviewed March 2015

Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition experience prickling or tingling sensations (paresthesias), numbness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, joints, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older. Weakness in the ankle muscles can make walking difficult. As the condition progresses, some people with hereditary sensory neuropathy type IA require wheelchair assistance.

Individuals with hereditary sensory neuropathy type IA typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected individuals cannot feel the pain of these sores, they may not seek immediate treatment. Without treatment, the ulcers can become infected and may require amputation of the surrounding area or limb.

Some people with hereditary sensory neuropathy type IA develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). Hearing loss typically develops in middle to late adulthood.

The signs and symptoms of hereditary sensory neuropathy type IA can begin anytime between adolescence and late adulthood. While the features of this condition tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are properly treated.

How common is hereditary sensory neuropathy type IA?

Hereditary sensory neuropathy type IA is a rare condition; its prevalence is estimated to be 1 to 2 per 100,000 individuals. 

What genes are related to hereditary sensory neuropathy type IA?

Mutations in the SPTLC1 gene cause hereditary sensory neuropathy type IA. The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes and play a role in many cell functions.

SPTLC1 gene mutations reduce the amount of functional SPTLC1 subunit that is produced, which results in an SPT enzyme with altered activity. This altered enzyme makes molecules called deoxysphingoid bases, which it does not normally produce. Because of this new function, the SPT enzyme's production of sphingolipid is reduced. Overall, there does not seem to be a decrease in sphingolipid production because the body is able to compensate for the SPT enzyme's reduced production. When accumulated, deoxysphingoid bases are toxic to neurons. The gradual destruction of nerve cells caused by the buildup of these toxic molecules results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type IA. Although the SPT enzyme does not produce a normal amount of sphingolipids, the body is able to compensate, and there does not seem to be an overall reduction of these fats in the body.

Read more about the SPTLC1 gene. 

How do people inherit hereditary sensory neuropathy type IA?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person has one parent with the condition. 

Where can I find information about diagnosis or management of hereditary sensory neuropathy type IA?

These resources address the diagnosis or management of hereditary sensory neuropathy type IA and may include treatment providers.
Gene Review: Hereditary Sensory Neuropathy Type IA
Genetic Testing Registry: Neuropathy hereditary sensory and autonomic type 1
Rare Diseases Clinical Research Network: Inherited Neuropathies Consortium
The Neuropathy Association: Diagnosing Neuropathy

You might also find information on the diagnosis or management of hereditary sensory neuropathy type IA in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about hereditary sensory neuropathy type IA?

You may find the following resources about hereditary sensory neuropathy type IA helpful. These materials are written for the general public.
MedlinePlus - Health information
Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases
Additional NIH Resources - National Institutes of Health
National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Fact Sheet

Educational resources - Information pages (9 links)

Patient support - For patients and families (4 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.
Gene Reviews - Clinical summary

Genetic Testing Registry - Repository of genetic test information (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog 

What other names do people use for hereditary sensory neuropathy type IA?

autosomal dominant hereditary sensory radicular neuropathy, type 1A
hereditary sensory and autonomic neuropathy, type IA
HSAN1A
HSAN IA
HSN1A
HSN IA

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about hereditary sensory neuropathy type IA?

Ask the Genetic and Rare Diseases Information Center. 

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.
What does it mean if a disorder seems to run in my family?
What are the different ways in which a genetic condition can be inherited?
If a genetic disorder runs in my family, what are the chances that my children will have the condition?
Why are some genetic conditions more common in particular ethnic groups?

These links provide additional genetics resources that may be useful.
Genetics and Health
Resources for Patients and Families
Resources for Health Professionals

http://ghr.nlm.nih.gov/condition/hereditary-sensory-neuropathy-type-ia