Hereditary Sensory Neuropathy

Summary

Hereditary neuropathies are the most prevalant group of hereditary disorders appearing in genetic counseling clinics, affecting approximately 1 in 2500 people. Sensory neuropathies account for some 10% of these disorders. Although rarely fatal, they do cause lifelong disabilities with significant social and economic impacts. No specific treatment currently available; however, we have developed a comprehensive management approach that has been widely adopted to compensate for distal weakness and sensory loss.

Although the causes of hereditary neuropathy are diverse, a common mechanism is responsible for the manifested disabilities: axonal degeneration. Axonal degeneration is significant in several disorders of the central nervous system, including multiple sclerosis and other common neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Axonal degeneration may stem from defects in axonal transport (Kamholz et al., 2000), failure of neurotrophin uptake (Bartlett et al., 1999, Ginty and Segal, 2002), or changes in sodium transport.

Dominantly inherited neurodegenerative disorders are generally caused by protein mutations that lead to cell toxicity, a gain of toxic function. We identified mutations in the protein, serine palmitoyltransferase (SPT) long chain subunit 1 (SPTLC1), that cause hereditary sensory neuropathy (HSN). In HSN, the mutant SPT enzyme is toxic, progressively impairing long nerve function first distally but eventually spreading to the whole nerve causing cell death. This is also described as a distal sensory and motor axonopathy.