Hereditary sensory and autonomic neuropathy type V

(often shortened to HSAN5)

Reviewed July 2011

What is HSAN5?

Hereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN5.

The signs and symptoms of HSAN5 appear early, usually at birth or during infancy. People with HSAN5 lose the ability to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ligaments, or muscles, is especially affected in people with HSAN5. Because of the inability to feel deep pain, affected individuals suffer repeated severe injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.

How common is HSAN5?

HSAN5 is very rare. Only a few people with the condition have been identified.

What genes are related to HSAN5?

Mutations in the NGF gene cause HSAN5. The NGF gene provides instructions for making a protein called nerve growth factor beta (NGFβ) that is important in the development and survival of nerve cells (neurons), including sensory neurons. The NGFβ protein functions by attaching (binding) to its receptors, which are found on the surface of neurons. Binding of the NGFβ protein to its receptor transmits signals to the cell to grow and to mature and take on specialized functions (differentiate). This binding also blocks signals in the cell that initiate the process of self-destruction (apoptosis). Additionally, NGFβ signaling plays a role in pain sensation. Mutation of the NGF gene leads to the production of a protein that cannot bind to the receptor and does not transmit signals properly. Without the proper signaling, sensory neurons die and pain sensation is altered, resulting in the inability of people with HSAN5 to feel pain.

Related Gene(s)

Changes in this gene are associated with hereditary sensory and autonomic neuropathy type V.

How do people inherit HSAN5?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of HSAN5?

These resources address the diagnosis or management of HSAN5 and may include treatment providers.

Genetic Testing Registry: Congenital sensory neuropathy with selective loss of small myelinated fibers (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0020075)

You might also find information on the diagnosis or management of HSAN5 in Educational resources (http://www.ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-v/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-v/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about HSAN5?

You may find the following resources about HSAN5 helpful. These materials are written for the general public.

MedlinePlus - Health information
- Health Topic: Degenerative Nerve Diseases (http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html)
- Health Topic: Peripheral Nerve Disorders (http://www.nlm.nih.gov/medlineplus/peripheralnervedisorders.html)
Additional NIH Resources - National Institutes of Health
- National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy (http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm)
- National Institutes of Health Rare Diseases Clinical Research Network: The Inherited Neuropathies Consortium (http://rarediseasesnetwork.epi.usf.edu/INC/professional/disorders/HSAN/)
Educational resources - Information pages
- National Institute of Neurological Disorders and Stroke: Hereditary Neuropathies (http://www.ninds.nih.gov/disorders/neuropathy_hereditary/neuropathy_hereditary.htm)
- Orphanet (http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=10856&Disease_Disease_Search_diseaseGroup=Hereditary-sensory-and-autonomic-neuropathy-type-2&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Hereditary-sensory-and-autonomic-neuropathy-type-5&title=Hereditary-sensory-and-autonomic-neuropathy-type-5&search=Disease_Search_Simple)
- University of Chicago Center for Peripheral Neuropathy (http://peripheralneuropathycenter.uchicago.edu/)
Patient support - For patients and families
The Neuropathy Association (http://www.neuropathy.org/site/PageServer)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Congenital sensory neuropathy with selective loss of small myelinated fibers (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0020075)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((hereditary%20sensory%20and%20autonomic%20neuropathy%20type%20v%5BTIAB%5D)%20OR%20(hsan%20type%20v%5BTIAB%5D)%20OR%20(hsan%20v%5BTIAB%5D)%20OR%20(hsan5%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/608654)

What other names do people use for HSAN5?

congenital insensitivity to pain
hereditary sensory and autonomic neuropathy, type 5
HSAN type V
HSAN V

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about HSAN5?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding HSAN5?

apoptosis ; autosomal ; autosomal recessive ; cell ; congenital ; gene ; growth factor ; joint ; mutation ; neuropathy ; perception ; protein ; receptor ; recessive ; sensory nerve ; tissue ; trauma

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Capsoni S, Covaceuszach S, Marinelli S, Ceci M, Bernardo A, Minghetti L, Ugolini G, Pavone F, Cattaneo A. Taking pain out of NGF: a "painless" NGF mutant, linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity. PLoS One. 2011 Feb 28;6(2):e17321. doi: 10.1371/journal.pone.0017321. (http://www.ncbi.nlm.nih.gov/pubmed/21387003?dopt=Abstract)
Einarsdottir E, Carlsson A, Minde J, Toolanen G, Svensson O, Solders G, Holmgren G, Holmberg D, Holmberg M. A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception. Hum Mol Genet. 2004 Apr 15;13(8):799-805. Epub 2004 Feb 19. (http://www.ncbi.nlm.nih.gov/pubmed/14976160?dopt=Abstract)
Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000 Jun;10(3):381-91. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10851172?dopt=Abstract)
Larsson E, Kuma R, Norberg A, Minde J, Holmberg M. Nerve growth factor R221W responsible for insensitivity to pain is defectively processed and accumulates as proNGF. Neurobiol Dis. 2009 Feb;33(2):221-8. doi: 10.1016/j.nbd.2008.10.012. Epub 2008 Nov 8. (http://www.ncbi.nlm.nih.gov/pubmed/19038341?dopt=Abstract)
Lewin GR, Mendell LM. Nerve growth factor and nociception. Trends Neurosci. 1993 Sep;16(9):353-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/7694405?dopt=Abstract)
Ritter AM, Lewin GR, Kremer NE, Mendell LM. Requirement for nerve growth factor in the development of myelinated nociceptors in vivo. Nature. 1991 Apr 11;350(6318):500-2. (http://www.ncbi.nlm.nih.gov/pubmed/2014050?dopt=Abstract)
Verhoeven K, Timmerman V, Mauko B, Pieber TR, De Jonghe P, Auer-Grumbach M. Recent advances in hereditary sensory and autonomic neuropathies. Curr Opin Neurol. 2006 Oct;19(5):474-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16969157?dopt=Abstract)
Verpoorten N, De Jonghe P, Timmerman V. Disease mechanisms in hereditary sensory and autonomic neuropathies. Neurobiol Dis. 2006 Feb;21(2):247-55. Epub 2005 Sep 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16183296?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.